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Before you operate, the ovarian mass has something important to say. Fortunately, we speak fluent cyst. OVA1 is an FDA-cleared* blood test to help you assess the probability that ovarian masses are malignant or benign prior to a planned surgery. When combined with a physician’s assessment, OVA1 achieved 6% sensitivity and 5% negative predictive value across a broad range of ovarian cancers.1 Adding OVA1 to your presurgical assessment may help determine whether referral to an oncologist is the best course of action. FOR MORE OVARIAN MASS TALKING POINTS, VISIT OVA-1.COM. magenta cyan yellow black ES112631_OBGYN0912_CVTP1_FP.pgs 08.21.2012 17:12 ADV How to order OVA1. OVA1 is available nationwide through Quest Diagnostics. TEST CODE: 16 1(X), 16 2(X) (includes FSH and LH to help determine menopausal status so that the appropriate reference range can be applied) SPECIMEN REQUIREMENTS: Test code 16 1(X): 2.2 mL refrigerated serum; 1.1 mL minimum Test code 16 2(X): 2.5 mL refrigerated serum; 1.3 mL minimum CPT CODES†: Test code 16 1(X): 84 Test code 16 2(X): 84 , 83001, 83002 ICD- CODES‡: 78 .33 78 .34 *FDA clearance does not denote official approval. The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payor being billed. † This is provided for informational purposes only and is not a guarantee of coverage. It is the provider’s responsibility to determine the appropriate codes. ‡ 12117 Bee Caves Road, Building III, Suite 100, Austin, TX 78738 Intended Use: OVA1 is a qualitative serum test that combines the results of 5 immunoassays into a single numerical result. It is indicated for women who meet the following criteria: over age 18, ovarian adnexal mass present for which surgery is planned, and not yet referred to an oncologist. OVA1 is an aid to further assess the likelihood that malignancy is present when the physician’s independent clinical and radiological evaluation does not indicate malignancy. Reference: 1. Ueland FR, Desimone CP, Seamon LG, et al. Effectiveness of a multivariate index assay in the preoperative assessment of ovarian tumors. Obstet Gynecol. 2011;117(6):128 -12 7. PRECAUTION: OVA1 should not be used without an independent clinical/radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of OVA1 carries the risk of unnecessary surgery, and/or delayed diagnosis. magenta cyan yellow black ES112630_OBGYN0912_CVTP2_FP.pgs 08.21.2012 17:12 ADV CONTEMPOR ARY OB / GYN SEPTEMBER 2012 , Vol. 57, No. 9 READ DR. LOCKWOOD’S INSIGHTS ON HEALTHCARE’S AGE OF UNCERTAINTY Translating TranslatingScience Scienceinto intoSound SoundClinical ClinicalPractice Practice ContemporaryOBGYN.net ContemporaryOBGYN.net Antenatal Imaging Challenges Detecting Congenital Diaphragmatic Hernia HE ALTHCARE’S AGE OF UNCERTAINT Y ◾ CONGENITAL DIAPHR AGMATIC HERNIA ◾ SURGICAL WOUNDS Anna K. Sfakianaki, MD, MPH Surgical Wounds Strategies for minimizing complications Jason Knight, MD and Pedro F. Escobar, MD ACOG GUIDELINES AT A GLANCE Management of Preterm Labor EFM MYTHBUSTERS Does FHR Increase Cesareans? SEPTEMBER 2012 | VOLUME 57, NUMBER 9 facebook.com/ContempOBGYN twitter.com/ContempOBGYN Congenital diaphragmatic hernia in the left hemidiaphragm. magenta yellow cyan black ES121147_obgyn0912_CV1.pgs 08.31.2012 05:55 ADV Translating Science into Sound Clinical Practice ContemporaryOBGYN.net Patrice M. Weiss, MD Thromboprophylaxis in pregnancy D. Ware Branch, MD SMFM CONSULT Prior classical cesarean Suneet P. Chauhan, MD JUNE 2012 | VOLUME 57, NUMBER 6 facebook.com/ContempOBGYN twitter.com/ContempOBGYN ContemporaryOBGYN.net Hyperemesis in pregnancy Taking a tiered approach Bleeding disorders: Impact on reproduction Andra James, MD Harness social media, enhance your practice David Seil Kim, MD, MS, MBA PROTOCOLS FOR HIGH-RISK PREGNANCIES Cervical insufficiency John Owen, MD, MSPH JULY 2012 | VOLUME 57, NUMBER 7 facebook.com/ContempOBGYN twitter.com/ContempOBGYN ACA IMPACT Editor-in-Chief ’s analysis Translating Science into Sound Clinical Practice ContemporaryOBGYN.net Postmenopausal HT Balancing risks and benefits Unzila A. Nayeri, MD POSTMENOPAUSAL HT ◾ SE X AND THE 50 -SOMETHING WOMAN ◾ HYSTEROSCOPIC MYOMECTOMY ◾ THYROID SCREENING Medical errors: Disclosure and apology Translating Science into Sound Clinical Practice CONTEMPOR ARY OB/GYN AUGUST 2012 , Vol. 57, No. 8 Proactive management strategies | Luis D. Pacheco, MD HYPEREMESIS ◾ BLEEDING DISORDERS AND REPRODUCTIVE HE ALTH ◾ HARNESSING SOCIAL MEDIA ◾ L ATE AND VARIABLE DECELER ATIONS MANAGING MATERNAL HEMORRHAGE ◾ DISCLOSING MEDICAL ERRORS ◾ THROMBOPROPHYL A XIS IN PREGNANCY ◾ CL ASSICAL CESARE AN Maternal hemorrhage CONTEMPOR ARY OB/GYN JULY 2012 , Vol. 57, No. 7 CONTEMPOR ARY OB/GYN JUNE 2012 , Vol. 57, No. 6 Translating Science into Sound Clinical Practice E Late FM MYT and va HBU riable STER decel S eratio ns Donna Shoupe, MD Sex and the 50-something woman Restoring satisfaction John E. Buster, MD CLINICIAN TO CLINICIAN Hysteroscopic myomectomy Pearls and pitfalls Morris Wortman, MD SMFM CONSULT Screening for thyroid disease in pregnancy AUGUST 2012 | VOLUME 57, NUMBER 8 facebook.com/ContempOBGYN twitter.com/ContempOBGYN Contemporary OB/GYN is a peer-reviewed journal that translates key advances in the specialty into excellence in day to day practice. Every issue delivers credible, relevant and timely reporting on the latest trends. • Practical, timely information from experts in the field • Peer-reviewed problem solving clinical articles • Editorial by Dr Charles Lockwood • Up-to-date clinical news and research • Diagnosis, treatment, and practice management information Begin your subscription today. ContemporaryObgyn.net/subscribe EDITOR IN CHIEF DEPUTY EDITOR Charles J Lockwood, MD, MHCM Jon I Einarsson, MD, MPH Dean of the College of Medicine and Vice President for Health Sciences, Associate Professor of Obstetrics and Gynecology, Harvard Medical School The Ohio State University Director, Division of Minimally Invasive Gynecologic Surgery, Brigham and Women’s Hospital COLUMBUS, OH BOSTON, MA YOUR EDITORIAL BOARD Haywood L Brown, MD Paula J Adams Hillard, MD Sharon T Phelan, MD Chair, Obstetrics and Gynecology Professor, Department of Obstetrics and Gynecology, Chief, Division of Gynecologic Specialties Professor, Department of Obstetrics and Gynecology Duke University Medical Center DURHAM, NC University of New Mexico Stanford University School of Medicine ALBUQUERQUE, NM STANFORD, CA Joshua A Copel, MD Sarah J Kilpatrick, MD, PhD Joe Leigh Simpson, MD Professor, Obstetrics, Gynecology, and Reproductive Sciences, and Pediatrics Chair, Department of Obstetrics and Gynecology, Executive Associate Dean for Academic Affairs, Professor of Obstetrics and Gynecology, and Human and Molecular Genetics Yale University School of Medicine Cedars-Sinai Medical Center LOS ANGELES, CA Florida International University College of Medicine NEW HAVEN, CT MIAMI, FL John O L DeLancey, MD Elloitt K Main, MD FOUNDING EDITOR Norman F Miller Professor of Gynecology, Director, Pelvic Floor Research, Group Director, Fellowship in Female Pelvic Medicine and Reconstructive Surgery Director, California Maternal Quality Care Collaborative, Chair and Chief, Department of Obstetrics and Gynecology Professor of Obstetrics and Gynecology University of Michigan Medical School California Pacific Medical Center John T Queenan, MD Georgetown University School of Medicine WASHINGTON, DC SAN FRANCISCO, CA ANN ARBOR, MI Robin Farias-Eisner, MD, PHD Laurie J McKenzie, MD Chief, Gynecology and Gynecologic Oncology, Department of Obstetrics and Gynecology, Director of the Center for Biomarker Discovery and Research Director of Oncofertility, Houston IVF, Director, UCLA Health System Houston Oncofertility Preservation and Education (H.O.P.E.) HOUSTON, TX LOS ANGELES, CA OUR MISSION For nearly a half century, busy practitioners have trusted Contemporary OB/GYN to translate the latest research into outstanding patient care. We are dedicated to providing them with evidence-based information on scientific advances in a clinically useful format. EDITORIAL Tulie O’Connor Group Editor, [email protected] Catherine M Radwan Senior Editor, [email protected] Julia Brown Editorial Assistant, [email protected] Aviva Belsky Renee Schuster Publisher List Account Executive 732-346-3044, [email protected] 440-891-2613, [email protected] Alison O’Connor National Account Manager 732-346-3075, [email protected] Joan Maley Miranda Hestor Account Manager Classified/Display Advertising Editorial Assistant, [email protected] 440-891-2722, [email protected] ART & PRODUCTION Joe Loggia Maureen Cannon Chief Executive Officer Permissions/International Licensing Tom Ehardt 440-891-2742, [email protected] Reprint Services Executive Vice President, Chief Administrative Officer 800-290-5460, ext. 100, [email protected] Georgiann Decenzo Jacqueline Moran AUDIENCE DEVELOPMENT Steve Sturm Robert McGarr Account Manager, Recruitment Advertising Joy Puzzo Group Art Director 440-891-2762, [email protected] Corporate Director, [email protected] Nicole Davis Gail Kaye Christine Shappell Art Director Terri Johnstone Sr. Production Manager SALES & MARKETING Director, Sales Data Director, [email protected] 732-346-3042, [email protected] Joe Martin Lisa Noble Manager, [email protected] Vice President, Group Publisher Sales Support 732-346-3017, [email protected] 732-346-3055, [email protected] SEPTEMBER 2012 magenta yellow cyan black Francis Heid Vice President, Media Operations Nancy Nugent Vice President, Human Resources Chief Information Officer 732-346-3060, [email protected] Hannah Curis Executive Vice President, Chief Marketing Officer J Vaughn Sr. Client Service Manager Ken Sylvia Executive Vice President CONTEMPORARY OB/GYN ES120260_obgyn0912_005.pgs 08.29.2012 11:31 5 ADV SEPTEMBER 2012 CONTEMPORARYOBGYN.NET VOL. 57, NO. 9 Translating Science into Sound Clinical Practice GRAND ROUNDS 26 Congenital diaphragmatic hernia ANNA K. SFAKIANAKI, MD, MPH Although relatively uncommon, CDH is a developmental delay that can result in severe neonatal complications and even death. Fortunately, antenatal ultrasound can help detect CDH, providing greater treatment options and outcomes for both patients and neonatals. 38 Surgical Wounds: Strategies for Minimizing Complications JASON KNIGHT, MD, AND PEDRO F. ESCOBAR, MD 26 Congenital diaphragmatic hernia in the left hemidiaphragm. Wound infection and wound separation are relatively common in the obstetric population. The keys to reducing the occurrence and severity of these complications are optimiation of host risk factors, preoperative preparation, surgical technique, and wound management. NEWSLINE 14 10 EDITORIAL CHARLES J. LOCKWOOD, MD, MHCM Healthcare’s Age of Uncertainty 20 LEGALLY SPEAKING DAWN COLLINS, JD Failure to timely diagnose complete placental abruption 54 EFM MYTHBUSTERS Fetal Heart Rate Monitoring and the Cesarean Delivery Rate SARAH J. KILPATRICK, MD, PHD ■ Safety of Vaginal Delivery for Preterm Birth Depends on Fetal Presentation ■ Cefixime No Longer Recommended for Treatment of Gonorrhea DAVID A. MILLER, MD This month’s article examines evidence underlying the common perception that EFM increases the cesarean delivery rate. ■ Bisphosphonates May Protect Against Breast Cancer ■ Obesity and Diabetes May Increase Risk of Orthopedic Surgical-Site Infections Management of preterm labor: Have we learned anything since 2003? 56 63 CLASSIFIED AD INDEX CONTEMPORARY OB/GYN (Print ISSN#0090-3159, DIGITAL ISSN#2150-6264), is published monthly by Advanstar Communications, Inc, 131 West First St, Duluth, MN 55806-2065. One-year subscription rates: $110.00 per year (USA and Possessions); $140.00 per year (elsewhere). Single copies (prepaid only) $12.00 in the USA; $18.00 per copy elsewhere. Include $6.50 per order plus $2.00 for US postage and handling. Periodicals postage paid at Duluth, MN 55806 and additional mailing offices. POSTMASTER: Please send address changes to Contemporary OB/GYN, PO Box 6084, Duluth, MN 55806-6084. Return Undeliverable Canadian Addresses to: Pitney Bowes, PO Box 25542, London, ON N6C 6B2, CANADA. Canadian GST number: R-124213133RT001. Publications Mail Agreement Number 40612608. Printed in USA. Subscription inquiries/address changes: toll-free 888-527-7008, or dial direct 218-740-6477. ©2012 Advanstar Communications Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including by photocopy, recording, or information storage and retrieval without permission in writing from the publisher. Authorization to photocopy items for internal/educational or personal use, or the internal/educational or personal use of specific clients is granted by Advanstar Communications Inc for libraries and other users registered with the Copyright Clearance Center, 222 Rosewood Dr, Danvers, MA 01923, 978-750-8400 fax 978-646-8700 or visit http://www. copyright.com online. For uses beyond those listed above, please direct your written request to Permission Dept, fax 440-756-5255 or email: [email protected]. 6 magenta yellow cyan black CONTEMPORARYOBGYN.NET SEPTEMBER 2012 ES120822_obgyn0912_006.pgs 08.30.2012 08:42 ADV COVER ILLUSTRATION BY MAYA SHOEMAKER, SHOEMAKER MEDICAL 48 ACOG GUIDELINES AT A GLANCE CONGENITAL DIAPHRAGMATIC HERNIA (CDH) KNOWING WHAT TO LOOK FOR MAY NOT BE EASY. KNOWING WHERE TO LOOK FOR HELP IS. About one in 2,500 fetuses is diagnosed with congenital diaphragmatic hernia (CDH), which if not treated successfully results in death or serious conditions. Texas Children’s Fetal Center is home to one of the most active and experienced CDH programs, employing protocol-based, multidisciplinary care, which results in documented optimal outcomes. CDH care at Texas Children’s begins with accurate and detailed diagnosis, which allows us to target therapy to each fetus’ unique morphologies for higher rates of success. Send us your toughest patients. We’re known for delivering. Learn more: fetal.texaschildrens.org or 1-877-FetalRx Left congenital diaphragmatic hernia with liver and intestines in the left chest and small, poorly developed lungs. magenta yellow cyan black ES110966_OBGYN0912_007_FP.pgs 08.20.2012 23:32 ADV Translating Science into Sound Clinical Practice ONLINE Part of the Your guide to what’s happening online at Contemporary OBGYN.net Y Contemporary OB/GYN is part of the ModernMedicine Network, a Web-based portal for health professionals offering best-in-class content and tools in a rewarding and easy-to-use environment for knowledge-sharing among members of our community. How social media can enhance your practice Bleeding Disorders: Impact on Reproduction Tiered approach to hyperemesis contemporaryobgyn.net/bleedingdisorder contemporaryobgyn.net/hyperemesis WHAT’S TRENDING The top ob/gyn clinical and practice management resources from ModernMedicine.com 1 2 More US minority women die in childbirth Minority women in the United States are more likely to die during or soon after childbirth than white women, according to a study from the CDC. 3 Medically unnecessary scheduled births cut A quality improvement program cut by 60% the number of deliveries scheduled a few weeks before the due date, a new paper reports. contemporaryobgyn.net/minority contemporaryobgyn.net/premature Variety could boost veggie eating More women choosing IUDs for birth control 4 Giving people a choice of vegetables at mealtimes got them eating more greens, but not fewer calories, says a new small study. A growing number of US women may be opting for IUDs as their birth control method, a national survey finds. 6 5 7 Ethical standards ignored A sizable share of egg donor organizations don’t adhere to ethical guidelines laid out by ASRM, according to a new study. contemporaryobgyn.net/ethics Like Us! Follow Us! 8 magenta yellow cyan black CONTEMPORARYOBGYN.NET Stress-induced heart symptoms most frequent in women over 55 Women are nearly nine times as likely as men to suffer stress-induced cardiomyopathy, and older women are at the highest risk, a new study of a large US national database has found. contemporaryobgyn.net/heart LEARN WHAT YOU’RE MISSING: Our online digital editions let you flip through the pages of your favorite Advanstar Communications publications from any computer. Sign up free at the following Web sites: ContemporaryPediatrics.com DrugTopics.com FormularyJournal.com facebook.com/ContempOBGYN twitter.com/ContempOBGYN Pregnant women who exercise and strengthen their pelvic muscles are less likely to have problems with urine leakage in their third trimester, a new clinical trials finds. contemporaryobgyn.net/kegel contemporaryobgyn.net/IUD contemporaryobgyn.net/veggies Kegel exercises curb incontinence in late pregnancy MedicalEconomics.com ManagedHealthcareExecutive.com PHOTOGRAPHER’S CHOICE RF/ADAM HESTER/GETTY IMAGES (TOP); BLEND IMAGES/JGI/JAMIE GRILL/GETTY IMAGES (BOTTOM LEFT); SCIENCE PHOTO LIBRARY/GETTY IMAGES (BOTTOM MIDDLE); COMSTOCK IMAGES/JUPITERIMAGES GETTY IMAGES (BOTTOM RIGHT) contemporaryobgyn.net/socialmedia SEPTEMBER 2012 ES119585_obgyn0912_008.pgs 08.28.2012 10:38 ADV Quicker and Easier 1 C-SECTION Tubal Ligation • No transection of tubes or surrounding tissue – reduced risk of bleeding • Excellent efficacy2 • The lowest incidence of ectopic pregnancy3,4 • Quicker and easier method compared to Pomeroy1 • Engineered to enclose thicker or swollen fallopian tubes • Also ideal for laparoscopic and post-vaginal delivery tubal ligations [Clips Shown Actual Size] 1. Kohaut, BA. et al. Randomized Trial to Compare Perioperative Outcomes of Filshie Clip vs. Pomeroy Technique for Postpartum and Intraoperative Cesarean Tubal Sterilization: A Pilot Study. Contraception. April 2004: 69(2004): 267-270. 2. Penfield, AJ. The Filshie Clip for Female Sterilization: A Review of World Experience. AJOG, March 2000, 182-3, 485,489. 3. Peterson, HB, et al. The Risk of Ectopic Pregnancy After Tubal Sterilization. The New England Journal of Medicine. March 1997. 4. Kovacs, et al. Female Sterilization with Filshie Clips: What is the risk of failure? A retrospective survey of 30,000 applications. J. of Family Planning and Reproductive Health Care. 2002: 28(1):34-3. magenta yellow cyan black To learn how the Filshie Tubal Ligation System can benefit you... and your patients, contact CooperSurgical at 800.243.2974 or 203.601.5200 or visit coopersurgical.com 81856 Rev. 03/11 ES119457_OBGYN0912_009_FP.pgs 08.28.2012 09:32 ADV BY CHARLES J. LOCKWOOD, MD, MHCM Healthcare’s Age of Uncertainty P hysicians should be no strangers to change. In my professional lifetime, we have gone from an era where solo practitioners were common to the ascendancy of large group practices to employment of physicians by medical systems.1 Payment systems have likewise evolved from unrestrained fee-for-service, to preferred provider schemes with heavily discounted fees, to pay for performance/value-based purchasing, even though the latter have, thus far, failed to substantially reduce costs. 2 We have also seen the rapid dissemination of electronic health records (EHRs). In 2009 only 1.5% of US hospitals had a comprehensive EHR, 3 but by 2013 it is projected that two-thirds will achieve “meaningful use” EHR capability.4 Now we must confront the Affordable Care Act (ACA) whose consequences cannot be fully predicted. Cost has been and will remain the overwhelming impetus for all these changes. Healthcare costs will soon be one of the largest contributors to national debt. 5 Even before the ACA’s expected increase in Medicaid enrollees, most individual states were struggling to cover the program’s expenses. Moreover, employee health insurance coverage is impeding US international industrial competitiveness.6 Far more fundamental healthcare changes are coming. From the Age of Uncertainty to the Age of Value So where do we go from here? Ultimately, healthcare delivery must and will evolve in conformity to basic WE WANT TO HEAR FROM YOU 10 magenta yellow cyan black Send your feedback to: [email protected]. CONTEMPORARYOBGYN.NET economic principles. Harvard Business School’s Michael Porter and colleagues have argued that healthcare delivery must be realigned to allow market forces to control cost and quality. They espouse the concept of value-based competition.7 Their definition of value is the quality of a patient’s outcome for a given medical condition relative to dollars expended over a full cycle of care. For acute care (such as myocardial infarction or childbirth) this latter interval might cover the span from diagnosis and treatment to initial rehabilitation. For chronic conditions (such as diabetes or endometriosis) a cycle of care would be a specific time interval such as 6 months. Porter advocates creating highly efficient, disease-specific “focus factories” wherein care is organized around a given disease with dedicated specialists, facilities, and staff. Payments for services by insurers would be bundled. They also envision full public reporting of outcomes and costs for such care. The principle f law in the Porter model is that medicine is not the same as fixing muff lers or Nearly a quarter of adults under age 65 and three-quarters of older adults have multiple comorbidities that together account for two-thirds of US health spending. SEPTEMBER 2012 ES119437_obgyn0912_010.pgs 08.28.2012 08:55 ADV It’s time to turn OAB on its head. OAB remains a problem for many patients As the number of patients diagnosed with overactive bladder (OAB) continues to grow, so does the need for improved prevention, diagnosis, and management.1 For many Americans now living with OAB, the disease can have a significant negative impact on their quality of life.2,3 Current OAB treatments may work well for some, but they are not for everyone.4 Why are many patients suffering despite current therapeutic options? One potential reason is lack of persistence with OAB therapy.5 While discontinuation of therapy is a significant issue among patients with chronic conditions, OAB therapy has demonstrated a higher rate of discontinuation compared with other drug classes.5 In a 2008 study investigating discontinuation rates of OAB therapy in the UK,* the median time to discontinuation was 4.76 months, with 77% of patients discontinuing their OAB treatment by 1 year.6 *A national health record database of women under the care of general practitioners in the UK (National Health Service).6 References: 1. Irwin DE, Kopp ZS, Agatep B, Milsom I, Abrams P. Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction. BJU Int. 2011;108:1132-1138. 2. Coyne KS, Sexton CC, Irwin DE, Kopp ZS, Kelleher CJ, Milsom I. The impact of overactive bladder, incontinence and other lower urinary tract symptoms on quality of life, work productivity, sexuality and emotional wellbeing in men and women: results from the EPIC study. BJU Int. 2008;101:1388-1395. 3. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20:327-336. 4. Benner JS, Nichol MB, Rovner ES, et al. Patient-reported reasons for discontinuing overactive bladder medication. BJU Int. 2009;105:1276-1282. 5. Yeaw J, Benner JS, Walt JG, Sian S, Smith DB. Comparing adherence and persistence across 6 chronic medication classes. J Manag Care Pharm. 2009;15:728-740. 6. Gopal M, Haynes K, Bellamy SL, Arya LA. Discontinuation rates of anticholinergic medications used for the treatment of lower urinary tract symptoms. Obstet Gynecol. 2008;112:1311-1318. © 2012 Astellas Pharma US, Inc. magenta yellow cyan black All rights reserved. Printed in USA 012F-500-5743 July 2012 ES110965_OBGYN0912_011_FP.pgs 08.20.2012 23:32 ADV EDITORIAL making cell phones. Healthcare costs do not follow normal supply and demand curves because the payor is separated from both the consumer and the provider. In addition, healthcare costs are not normally distributed as in a consumer market, but fall in a highly asymmetrical pattern across the population. For example, in the United States, 1% of patients account for 22% of costs and 5% account for 50% of costs with almost all these patients having multiple comorbidities. 8 In fact, nearly a quarter of adults under age 65 and three-quarters of older adults have multiple comorbidities that together account for two-thirds of US health spending.9 Thus, Porter’s single-disease focus factories would poorly address patients who account for two-thirds of costs. Addressing this problem requires an acceptance that healthcare is a highly complex, nonlinear system and that potential remedies often have unanticipated and undesired effects.10 Currently, the highly discounted, fee-for-service payment system demonstrates this as it encourages unnecessary care and procedures for healthy patients to make up for discounts, while discouraging coordination of care for the very patients responsible for most of the cost. Ironically, complex systems follow rather simple rules. For example, Lipitz argues that simply changing our payment system to global fees would facilitate more effective interactions and the necessary self-organizing behavior among providers to reduce unnecessary care and increase coordination.10 So what would the ensuing care delivery paradigm look like? Cost has been and will remain the overwhelming impetus for all these changes. The three tiers of future healthcare I envision future healthcare to be a three-tier system. The first tier, the base of the healthcare delivery pyramid, would provide relatively healthy children and adults access to sporadic low-acuity and basic preventative care. Tier 1 ref lects the notion of innovative healthcare disruptions espoused by another Harvard Business School professor, Clay Christensen.11 Tier 1 providers would include registered nurses, nurse practitioners (NPs), physician assistants (PAs), and midwives providing 12 magenta yellow cyan black CONTEMPORARYOBGYN.NET acute, low-complexity ambulatory care by applying algorithm-based pathways (such as ruling out strep throat, upper respiratory tract infections, and evaluating simple pediatric conditions) and offering basic wellness and prevention services (such as vaccines, diet counseling, breast exams, and Pap smears). They would see “walk-in” patients for nominal fees, in easily accessible offices based in retail stores, pharmacies, or freestanding community offices. All these providers would be electronically and operationally linked to a health system’s primary care medical homes and multispecialty care medical homes. The former would constitute the second tier of this health system and comprise a mix of general internal and family medicine doctors, general surgeons, general ob/gyns, and pediatricians as well as optometrists, dentists, and mental health professionals. Care would be provided in teams that also include physician extenders: NPs, PAs, midwives, dieticians, and physical and occupational therapists. Here the focus would be on wellness and advanced prevention as well as the detection and management of common medical, surgical, and reproductive health conditions (such as uncomplicated hypertension, diabetes, obesity, uncomplicated joint replacement, pregnancies, contraception, abnormal uterine bleeding). The critical function of tier 2 providers would be to address a variety of healthcare needs—behavioral, social, physical, and environmental—before they push patients into the third tier. Tier 2 could not function without tier 1 because we simply do not have sufficient primary care capacity. So much of a primary care physician’s (PCP) time is currently taken up by unnecessary low-acuity care that today PCPs would need to work 18-hour days to adequately care for an average panel of patients.12 Moreover, implementation of the ACA will only exacerbate this PCP shortage. Two years after healthcare reform was implemented in Massachusetts by Governor Romney, along lines virtually analogous to the ACA, wait times for PCPs averaged 36 days for family medicine and 48 days for internal medicine.12 Thus, by siphoning off the 30% to 40% of low-acuity care currently congesting primary care offices and making better use of interprofessional teams, we can better accommodate US primary care needs. Tier 3 focuses on the 5% to 10% of patients who account for more than two-thirds of US healthcare costs. Thus, once a patient is identified as having SEPTEMBER 2012 ES119439_obgyn0912_012.pgs 08.28.2012 08:55 ADV EDITORIAL a refractory medical disorder, a complex surgical requirement, or multiple comorbidities, he or she would be referred to a multispecialty-based medical home. This would comprise a cluster of Porter’s highly efficient focus factories specializing in one condition (such as insulin-dependent diabetes, lupus, multiple sclerosis, renal disease, high-risk obstetrics, infertility, urogynecologic issues, or cancer). Patients with comorbidities would have their care coordinated by “comprehensivists” who Tinetti, et al define as generalists with expertise and experience in caring for complex patients with multiple chronic conditions.9 Computer algorithms would be leveraged to identify this high-risk cohort (so-called hotspotting) and decision-support software used to optimize care. Tier 3 patients are those most in need of personalized medicine supported by home visits as well as technology portals such as direct physician Web access, telemedicine, and frequent provider phone contact, all of which can afford such patients immediate access to healthcare resources in their homes and communities. Tier 3 facilities would be either community-based or part of a medical center, depending on acuity. this transition are already occurring: 1) consolidation of physicians and hospitals into large integrated systems; 2) dissemination of EHRs; and 3) increasing public disclosure of patient outcomes and satisfaction, and health system costs. Thus, we are already poised to transition from the age of healthcare uncertainty to the age of healthcare value. Take-home message 10. Lipsitz LA. Understanding health care as a complex system: the foundation for unintended consequences. JAMA. 2012;308(3):243-244. All these providers would be electronically and operationally linked to a health system’s primary care medical homes and multispecialty care medical homes. Healthcare is a complex system whose current perverse economic incentives decouple payors from those that receive and provide care. The result is unsustainable costs. But as mentioned earlier, complex systems follow simple rules, and changing the payment system to restore market forces by ensuring providers are mindful of both cost and outcome will promote necessary self-organization by hospital systems and caregivers to reduce unnecessary care and errors and increase coordination and consistency of care. My guess is that this will lead to 3 tiers of care, each designed to optimize outcomes while minimizing costs. The critical initial steps in REFERENCES 1. O’Malley AS, Bond AM, Berenson RA. Rising hospital employment of physicians: better quality, higher costs? Issue Brief Cent Stud Health Syst Change. 2011;(136):1-4. 2. Congressional Budget Office. Lessons from Medicare’s Demonstration Projects on Disease Management, Care Coordination, and Value-Based Payment. Issue Brief. http://www.cbo.gov/doc.cfm?index=12663. Published January 2012. Accessed August 5, 2012. 3. Jha AK, DesRoches CM, Campbell EG, et al. Use of electronic health records in U.S. hospitals. N Engl J Med. 2009;360(16):1628-1638. 4. Jha AK, Burke MF, DesRoches C, et al. Progress toward meaningful use: hospitals’ adoption of electronic health records. Am J Manag Care. 2011;17(12 spec no.):SP117-SP124. 5. Keehan SP, Sisko AM, Truffer CJ, et al. National health spending projections through 2020: economic recovery and reform drive faster spending growth. Health Aff (Milllwood). 2011;30(8):1594-1605. 6. Johnson T. Healthcare Costs and U.S. Competitiveness. Council on Foreign Relations Web site. http://www.cfr.org/health-science-andtechnology/healthcare-costs-us-competitiveness/p13325. Updated March 26, 2012. Accessed August 14, 2012. 7. Porter ME, Teisberg EO. Redefining Health Care: Creating Value-Based Competition on Results. Boston, MA: Harvard Business School Press; 2006. 8. Kennedy K. 5% of patients account for half of health care spending. USA Today. http://www.usatoday.com/news/washington/story/2012-01-11/ health-care-costs-11/52505562/1. Published January 11, 2012. Updated January 12, 2012. Accessed August 5, 2012. 9. Tinetti ME, Fried TR, Boyd CM. Designing health care for the most common chronic condition—multimorbidity. JAMA. 2012;307(23):2493-2494. Erratum in: JAMA. 2012;308(3):238. 11. Christensen CM, Grossman JH, Hwang J. The Innovator’s Prescription: A Disruptive Solution for Health Care. New York: McGraw-Hill: 2009. 12. Ghorob A, Bodenheimer T. Sharing the care to improve access to primary care. N Engl J Med. 2012;366(21):1955-1957. DR LOCKWOOD, Editor in Chief, is Dean of the College of Medicine and Vice President for Health Sciences at The Ohio State University, Columbus, Ohio. SEPTEMBER 2012 magenta yellow cyan black CONTEMPORARY OB/GYN 13 ES119438_obgyn0912_013.pgs 08.28.2012 08:55 ADV News you can use from the name you trust Safety of Vaginal Delivery for Preterm Birth Depends on Fetal Presentation Some studies indicate that planned cesarean delivery may reduce neonatal mortality compared with vaginal delivery for early preterm births. Te safety of vaginal delivery in this scenario may depend on vertex versus breech presentation, however, according to a recent retrospective, multicenter cohort study. Te Consortium on Safe Labor study looked at maternal and fetal data on 228,668 deliveries between 2002 and 2008, based on medical records for all singleton deliveries at ≥24 to <32 weeks’ gestation from 4352 pregnancies. Precursors to delivery were classified as preterm labor, preterm premature rupture of membranes, or indicated delivery. In a subgroup of 2906 pregnancies, neonatal outcomes were assessed afer attempted vaginal delivery versus planned cesarean delivery, subdivided by gestational age (24 to 27 versus 28 to 31 weeks). Neonatal outcomes differed by fetal presentation. For vertex presentations at 24 to 27 weeks, vaginal delivery was attempted in 77% of cases and produced no significant differences in death rates compared with planned cesarean (mortality 15.2% versus 13.5%, respectively; P=0.581). Vaginal delivery therefore was successful in 85% of cases. Breech presentations, 14 magenta yellow cyan black contemporaryobgyn.net however, were less likely to be delivered vaginally (32%), and vaginal delivery was associated with a higher mortality rate (25.2% versus 13.2%; P=0.003). Breech pregnancies with planned cesarean delivery were more likely to be complicated by neonatal sepsis and need for ventilation (both P<0.05). Findings were similar at 28 to 31 weeks, with no significant differences in neonatal mortality between vaginal and cesarean vertex deliveries (2.2% versus 3.1%; P=0.347), but significantly higher mortality for vaginal versus cesarean breech deliveries (6.0% versus 1.5%; P=0.016). In the vertex group, cesarean was associated with higher risks of respiratory distress syndrome, neonatal ventilation, and asphyxia, but a lower rate of intraventricular hemorrhage (all P<0.05). Multivariate analyses confi rmed that vertex deliveries incurred no differences in neonatal mortality by delivery method at either gestational interval. Breech presentations, however, had an increased risk of mortality with attempted vaginal delivery both at 24 to 27 weeks (relative risk [RR] 3.0; 95% confidence interval [CI], 1.8-5.1) and 28 to 31 weeks (RR 5.1; 95% CI, 1.3-19.9). When advising women at <32 weeks’ gestation, practitioners should be aware that vaginal delivery is just as safe as cesarean delivery for vertex presentations, but planned cesarean reduces neonatal mortality for breech presentations. reddy uM, Zhang J, Sun L, Chen Z, raju TN, Laughon SK. Neonatal mortality by attempted route of delivery in early preterm birth. Am J Obstet Gynecol. 2012;207(2):117.e1-e8. Cefixime No Longer Recommended for Treatment of Gonorrhea Te spread of antimicrobial resistance has claimed another victim. According to the Centers for Disease Control and Prevention (CDC), gonorrhea should no gETTY iMAgES/THE AgENCY COLLECTiON/gOLDMuND LuKiC NEWS LINE september 2012 ES119694_obgyn0912_014.pgs 08.28.2012 11:44 ADV magenta yellow cyan black ES110958_OBGYN0912_015_FP.pgs 08.20.2012 23:32 ADV NEWSLiNE update to CDC’s Sexually Transmitted Diseases Treatment guidelines, 2010: Oral Cephalosporins No Longer a recommended Treatment for gonococcal infections. Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep. 2012;61:590-594. expert commentary: this is an important advisement for ob/gyns, and yet another sign that antimicrobial resistance will be a major challenge in this new century. the take-home point is that uncomplicated urogenital, anorectal, or pharyngeal gonorrhea should be treated with combination therapy with ceftriaxone 250 mg intramuscularly plus either azithromycin in a single dose of 1 g orally or doxycycline at 100 mg orally twice a day for 1 week. test of cures should include sensitivity testing. - charles J. Lockwood, mD, mHcm 16 magenta yellow cyan black contemporaryobgyn.net Bisphosphonates May Protect Against Breast Cancer Research has shown that use of bisphosphonates for bone loss may be associated with reduced risk of breast cancer recurrence, but the role of treatment duration is unclear. In fact, according to a recent meta-analysis, bisphosphonate therapy may decrease breast cancer risk for as long as treatment continues. Investigators searched the medical literature through June 2011 for studies of the association between bisphosphonate use and breast cancer risk that included, or allowed the calculation of, relative risks (RRs) and 95% confidence intervals (CIs). Four studies were ultimately used for data extraction and synthesis. Risk was evaluated for any use of bisphosphonates and per 1-year increase in bisphosphonate use compared with nonusers. Te publications were 2 cohort studies and 2 retrospective case-control studies from 2010 and 2011 that included a total of 15,363 breast cancer patients and 84,931 bisphosphonate users. Among the 3 studies that listed the relevant medications, alendronate was the most common bisphosphonate (52% to 90%). Women who used any type of bisphosphonate had a 15% reduction in risk of breast cancer compared with nonusers (pooled RR 0.85; 95% CI, 0.74-0.98), and the reduction was even greater, at 32%, when the analysis was restricted to patients with invasive tumors gETTY iMAgES/FLiCKr/ANNETTE BuNCH longer be treated with cefi xime as a fi rst-line therapy. Te CDC updated its treatment guidelines in the August 10 issue of Morbidity and Mortality Weekly Report. Neisseria gonorrhoeae is highly prevalent and an important cause of pelvic inflammatory disease, ectopic pregnancy, infertility, and the spread of HIV infection. Te CDC conducts periodic gonorrhea surveillance through its Gonococcal Isolate Surveillance Project. Laboratory studies for 2006-2011 indicate that urethral N gonorrhoeae has developed resistance to cefi xime, which is therefore no longer recommended at any dose for fi rst-line therapy. Instead, the CDC states that uncomplicated urogenital, anorectal, or pharyngeal gonorrhea should be treated with combination therapy with cef riaxone 250 mg intramuscularly plus either azithromycin in a single dose of 1 g orally or doxycycline at 100 mg orally twice a day for 1 week. Treatment failure should be addressed by culture and antimicrobial susceptibility testing. Cefi xime and other medications can be considered as second-line agents, followed by a test-ofcure 1 week later. Sex partners also require treatment. Supporting data for the new recommendations include elevations in cefi xime minimum inhibitory concentrations (MICs) in men. Between 2006 and 2011, the proportion of isolates with elevated MICs (≥0.25 μg/mL) increased significantly, especially in men who have sex with men and in the western United States. Te need for the guideline revision comes as no surprise, given that N gonorrhoeae has previously developed resistance to fluoroquinolones, prompting the CDC to recommend cephalosporins instead, and the recent discovery of declining effectiveness of cefi xime. CDC hopes that the restriction of cefi xime use will also delay the development of resistance to cef riaxone. september 2012 ES119693_obgyn0912_016.pgs 08.28.2012 11:44 ADV CA125 + HE4 The new formula for diagnostic clarity of ovarian cancer From the company that brought you CA125, Fujirebio Diagnostics brings you HE4, the first FDA-cleared biomarker in 25 years for ovarian cancer management. • Serum concentrations of HE4 are not increased in patients with endometriomas and other types of endometriosis as compared to CA125 1 • Better assessment of adnexal masses: when combined with physician assessment, the Risk of Ovarian Malignancy Algorithm (ROMA) correctly stratified women with epithelial ovarian cancer and women with benign disease 2 • In a study of nine biomarkers, CA125 + HE4 was found to be most sensitive for ovarian cancer 3 • Unique CPT code and Medicare reimbursable • Vast body of multi-national peer-reviewed and published clinical evidence supporting the use of HE4 To better assess adnexal mass CA125 + HE4 adds up to increased diagnostic clarity. PRECAUTION: ROMA (HE4 EIA + ARCHITECT CA125 II) should not be used without an independent clinical/radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of ROMA (HE4 EIA + ARCHITECT CA125 II) carries the risk of unnecessary testing, surgery, and/or delayed diagnosis. For more information visit: www.he4test.com The Risk of Ovarian Malignancy Algorithm (ROMA™) is a qualitative serum test that combines the results of HE4 EIA, ARCHITECT CA125 II™ and menopausal status into a numerical score. ROMA is intended to aid in assessing whether a premenopausal or postmenopausal woman who presents with an ovarian adnexal mass is at high or low likelihood of finding malignancy on surgery. ROMA is indicated for women who meet the following criteria: over age 18; ovarian adnexal mass present for which surgery is planned, and not yet referred to an oncologist. ROMA must be interpreted in conjunction with an independent clinical and radiological assessment. This test is not intended as a screening or stand-alone diagnostic assay. 1 Huhtinen K, Suvitie P, Hiissa J, et al. Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. Br J Cancer. 2009;100:1315-1319. ROMA (HE4 EIA + ARCHITECT CA125 II), Ref. No. 404-10US [instruction for use]. Göteborg, Sweden: Fujirebio Diagnostics, 2011. Moore RG, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecol Oncol. 2008;108:402-408. FDI-352 Rev. 10/11 2 3 magenta yellow cyan black ES111015_OBGYN0912_017_FP.pgs 08.20.2012 23:34 ADV Looking for the Lowest Pain Procedure for In-Office Endometrial Ablation? In recent clinical studies, Her Option ranked lowest in patient pain for in-office endometrial ablation procedures.1, 2 Choose the procedure that’s effective, safe and well tolerated by your patients. NO PAIN 1 SEVERE PAIN 2 3 4 5 HerOption 1.12 6 7 ThermaChoice 6.56 8 9 10 NovaSure 7.76 (pooled RR 0.68; 95% CI, 0.59-0.80). A dose-response relation was found, whereby for each additional year of bisphosphonate use, women had a reduced risk of breast cancer (pooled RR 0.92; 95% CI, 0.87-0.96) compared with nonusers. Te benefit seemed to appear afer at least 1 year of use, which gave a significant reduction in risk (P<0.001); results for treatment of less than 1 year were insignificant (P=0.51). Bisphosphonates therefore appear to reduce risk of any breast cancer diagnosis and, in particular, risk of invasive tumors. Te authors acknowledge the limitations of meta-analyses and state that randomized controlled trials are needed before bisphosphonates can be prescribed for prevention of breast cancer. Liu Y, Zhao S, Chen W, et al. Bisphosphonate use and the risk of breast cancer: a meta-analysis of published literature. Clin Breast Cancer. 2012;12(4):276-281. Obesity and Diabetes May Increase Risk of Orthopedic Surgical-Site Infections Diabetes is known to be associated with infectious complications afer orthopedic procedures, and a recent study indicates that obesity and diabetes are independent risk factors for postoperative surgical-site infections (SSIs). Te study, performed in a Finnish hospital specializing in joint replacement, explored the effects of obesity and diabetes on infection rates afer primary hip and knee replacement procedures. Tis populationbased series included 7181 hip and knee replacements performed for osteoarthritis between 2002 and 2008. Plasma glucose was measured repeatedly before and 18 magenta yellow cyan black contemporaryobgyn.net during the hospital stay, and hyperglycemia was defined as glucose ≥6.9 mmol/L (124 mg/dL). Patients were evaluated prospectively for the occurrence of periprosthetic joint infection during the year afer surgery. Joint infections were diagnosed afer 52 procedures (0.72%). Morbid obesity (≥40 kg/m2) was associated with significantly more infections than was normal body weight (<25 kg/m2), with infection rates of 4.66% versus 0.37%, respectively. Morbid obesity remained significant in multivariate analysis (OR 6.4; 95% CI, 1.7-24.6), although intermediate levels of obesity (25-29, 30-34, and 35-59 kg/m2) were not significant. Hip replacements in morbidly obese patients were associated with a 30fold elevation in infection risk, and knee replacements with an 8-fold increase. Patients with diabetes diagnosed before surgery had an elevated infection risk independent of obesity (OR 2.3; 95% CI, 1.1-4.7). However, morbidly obese patients with diabetes had the highest infection rate (9.8%). Jämsen E, Nevalainen P, Eskelinen A, Huotari K, Kalliovalkama J, Moilanen T. Obesity, diabetes, and preoperative hyperglycemia as predictors of periprosthetic joint infection: a single-center analysis of 7181 primary hip and knee replacements for osteoarthritis. J Bone Joint Surg Am. 2012;94(14):e1011-e1019. gETTY iMAgES/VETTA/HuSEYiN TuNCEr Visual Analog Scale (VAS) september 2012 ES119701_obgyn0912_018.pgs 08.28.2012 11:45 ADV Maximum Patient Comfort Lowest Complication Rate 1,2 Shown Actual Size Ultra-Slim 5.5 mm Probe 3 Scan. Watch. Learn... about the Her Option Procedure The Best Choice for In-Office Endometrial Ablation Procedures • Exceptional patient outcomes...high patient satisfaction 4 • Short and efficient total treatment time from pre-procedure to recovery • Sub-zero temperature provides a natural analgesic effect 5 • No intravenous sedation required To find out how Her Option can benefit your practice...and your patients, call 800.243.2974 or visit www.HerOption.com 1,2, 3, 4, 5 for reference details see http://www.coopersurgical.com/Documents/HerOptionBrochure.pdf 81788 Rev. 01/12 © 2012 CooperSurgical, Inc. magenta yellow cyan black ES119459_OBGYN0912_019_FP.pgs 08.28.2012 09:32 ADV BY DAWN COLLINS, JD R IS K M A N AGEM EN T I N O B S T E T R I C S A N D GY N ECO LO GY Failure to timely diagnose complete placental abruption went to the hospital with abdominal pain during her 36th week of pregnancy. No fetal heart tones were heard and after a nurse performed a sonogram, the woman was told that the baby had died in utero. She told her treating physician that she was still feeling movements and he performed an ultrasound (U/S). He then sought a radiology confirmation of the diagnosis of fetal demise. Seventy-five minutes later an U/S technician arrived and immediately identified a still-beating heart. A complete placental abruption was seen. The fetus was delivered and transferred to another hospital with hy pox ic-ischem ic encephalopathy and survived with cerebral palsy. The patient sued those involved with the delivery, claiming negligence in t hat the U/S equipment was old, the wrong ty pe of transducer was used, and an U/S technician more familiar with using more advanced U/S equipment should have been available immediately. The physician argued that he was certain that the fetal heart had stopped when he performed the U/S and that the heart had started again by the time the U/S technician found a heartbeat. A PENNSYLVANIA WOMAN The hospital was at fault for not providing up-todate equipment and not having skilled personnel. LEGAL PERSPECTIVE The jury in this case found no negligence on the part of the physician, but did find that the hospital was at fault for not providing up-to-date equipment and not 20 magenta yellow cyan black CONTEMPORARYOBGYN.NET having skilled personnel to perform an emergency U/S in a timely manner. The jury awarded a total of $78.5 million, which included $1.5 million in emotional distress for the mother, $10 million in pain and suffering for the child, $2 million in lost future earnings, and the rest in future medical expenses. Complications after amniocentesis results in cerebral palsy A VIRGINIA WOMAN was 33 weeks pregnant when she was found to have gestational diabetes. She was referred to an obstetrician who planned to induce labor 2 to 3 weeks early if the fetus grew too large, to reduce the risk of injury during delivery. An amniocentesis was done to check fetal lung maturity. A second obstetrician noted some abnormality of the fetal heart rate (FHR) following the procedure and directed the patient’s family practitioner to induce labor and go ahead with delivery. The infant had seizures after delivery, was determined to have brain damage because of lack of oxygen, and had no kidney function. She has undergone 2 kidney transplants and has cerebral palsy. At time of trial she was aged 10 years and functioning at prekindergarten level. In the lawsuit that followed the birth, the patient alleged that she was not fully informed of the risks and alternatives of the amniocentesis. She claimed that complications arose during the procedure and the physician failed to stop the amniocentesis and postpone the testing. She maintained that an immediate cesarean delivery should have been performed. The defense denied any negligence, arguing that their care was an appropriate alternative plan to the actions the patient claimed should have been taken. A $9 million verdict was returned. SEPTEMBER 2012 ES119665_obgyn0912_020.pgs 08.28.2012 11:41 ADV LEGALLY SPEAKING LEGAL PERSPECTIVE In this case, the family practitioner and the hospital reached prior settlements with the plaintiff and the trial went ahead against the obstetricians involved with the amniocentesis and the post-procedure FHR monitoring. The $9 million award included $7 million for the child and $2 million for the mother. In Virginia, however, there is a cap that limits the recoverable amount to $1.6 million for each plaintiff. This cap amount was then reduced by the settlement agreement and thus the setoff made the final amount available $1.4 million for each. Bowel perforation during oophorectomy not detected A N E W YO R K WO M A N in her 40s underwent an oophorectomy. The procedure was performed by her gynecologist, who also removed a benign tumor that was in the patient’s abdomen and dissolved an adhesion that joined the bowel and the wall of the abdomen. The patient developed postsurgical pain but was discharged. Three days after the procedure she was readmitted and diagnosed with a perforation of the bowel. She underwent drainage and surgery to close the perforation. She has a scar on her abdomen from the second operation and claimed that her abdomen remained tender. The woman sued her gynecologist and those involved with her surgery, claiming the defendant physician was negligent in perforating the bowel during the surgery and failed to provide proper postoperative care. She alleged the bowel perforation should have been detected during surgery by inspection of the bowel and she should not have been discharged with the complaint of pain. The defendant physician claimed the patient had sustained only a small perforation that was easily overlooked during intraoperative inspection and that the bowel was properly inspected. The defendants claimed that the patient’s postsurgical pain was normal and that she had requested a full meal. A defense claim also was made that the plaintiff ’s symptoms did not worsen until the day after discharge and that she did not report this for 9 to 12 more hours. The defense alleged that the patient’s continuing pain was from a preexisting condition unrelated to the surgery and that her physical limitations were related to a knee injury that occurred 2 years after the oophorectomy. A defense verdict was returned. Failure to remove catheter during delivery results in incontinence A 31-YEAR-OLD KENTUCKY WOMAN went to the hospital for delivery of her first child. After a long and difficult labor, her obstetrician performed the delivery with the use of forceps. The infant had no problems. The patient, however, has suffered incontinence since the delivery. Despite several repair surgeries, the condition continues and she is required to wear pads for the incontinence. The woman sued those involved with the delivery and claimed the physician was negligent in failing to remove a fully inf lated Foley catheter before beginning the delivery, which led to a urethral sphincter injury. The physician claimed that the decision regarding whether to remove the catheter was a matter of hospital policy and rested with the nursing staff, and also questioned if the catheter had been properly placed. The matter was initially dismissed because of the plaintiff ’s failure to respond to discovery requests, but that decision was overturned on appeal. The matter moved to trial and a defense verdict was returned. Necrotizing fasciitis after cesarean myomectomy surgery A 39-YEAR-OLD WOMAN was admitted to a Michigan hospital for cesarean delivery because of preeclampsia. Immediately after the delivery of the infant, the attending obstetrician performed a myomectomy. The patient was hospitalized for several days and on t he day prior to her discharge, her incision opened and clear drainage was noted. The day after her discharge from the hospital, she went to an emergency department with complaints of intense abdominal pain. Necrotizing fasciitis was diagnosed and debridement surgery was performed. She was t hen transferred to another hospital, but died several days later from the infection. A lawsuit was filed on her behalf, cla iming t hat t he obstetricians should not have performed a my om e c t omy at the same time as the cesarea n deliver y a nd t hat doi ng so caused the infection. It was a lso a l leged t hat prophylac t ic antibiotics should have been prescribed at the time of surgery to prevent an infection, and that the physicians failed to recognize the signs and symptoms of the infection before discharging the patient from The defense maintained that prophylactic antibiotics for cesarean delivery procedures are not the standard of care. SEPTEMBER 2012 magenta yellow cyan black CONTEMPORARY OB/GYN 21 ES119666_obgyn0912_021.pgs 08.28.2012 11:41 ADV Women need no longer ignore Vaginal Dryness... a major cause of vaginitis and unpleasant odors A Better Alternative to Estrogen Therapy Glycerin & Paraben - Free For more information visit: www.luvenacare .com magenta yellow cyan black ES119576_OBGYN0912_022_FP.pgs 08.28.2012 10:32 ADV ® LUVENA PREBIOTIC - the first feminine moisturizer to support the body’s own bio-ecosystem defenses found normally in the vagina. LUVENA® PREBIOTIC Moisturizer/Lubricant ™ utilizes natural GLYCOGEN and MANNOSE Prebiotic formula to support the healthy flora balance of the vagina - combined with a proven LPG Enzyme System to inhibit “harmful” bacterial growth. Think of LUVENA® PREBIOTIC as a “bio-shield“, working with the body to protect women against harmful bacterial growth associated with common vaginal problems due to dryness. How LUVENA® PREBIOTIC works and why every woman can benefit. The enzymes in LUVENA inhibit harmful bacteria and yeast such as candida albicans. Long lasting moisture barrier helps in soothing irritations. ABNORMAL VAGINA • Dry Irritations • Excessive Bacteria • Odors Key prebiotic agents to promote “good” bacteria growth, mainly Acidophilus. NORMAL VAGINA • Healthy Tissues • Balanced Microflora • Correct pH Especially designed for those women: Regular use helps: • Prone to yeast infections caused by antibiotics Restore essential moisture • With autoimmune disorders such as diabetics, lupus and sjogren’s syndrome causing dryness • Peri / post Menopausal having changes in vaginal environment with a reduction of natural moisture Reduce unpleasant odors Promote healthy flora balance and pH Protect against vaginal irritations • Taking medications causing dryness or changes in fluid The prebiotic for a dry vagina. NEW! Anti-itch Feminine Wipes with natural bio-active odor fighting enzymes • Effective and gentle cleaning • Cooling comfort and freshness between showers magenta yellow cyan black ES119575_OBGYN0912_023_FP.pgs 08.28.2012 10:32 ADV LEGALLY SPEAKING the hospital. It was also argued that the patient was not fully informed of the risks of performing both surgeries at the same time. The obstetricians claimed that the patient was fully informed of the risks of surgery and that it was reasonable to perform a myomectomy immediately following a cesarean delivery. They also argued that she had no signs or symptoms of infection after the surgery and that 30% of cesarean incisions can open after the procedure. The defense maintained that prophylactic antibiotics for cesarean delivery procedures are not the standard of care and that her infection was a rapidly spreading, rare bacteria. A defense verdict was returned. Colon perforation during electrocauterization of adhesions A N I N D I A N A W O M A N was diagnosed w it h mi ld cervical dysplasia following a Pap smear. She was t re at e d by her g y ne c olog i s t , w ho p er for me d colposcopy and confirmed the diagnosis. He then recommended she have Pap smears every 3 months for the next year. The patient was seen several times over the subsequent months with complaints of pain in her left side. Six months later her exam revealed stage I endometriosis, and her gynecologist used bipolar forceps to eradicate the endometriosis cells. He then prescribed a course of Lupron injections for the next 5 months, followed by hormonal suppression using birth control pills. The patient had relief for 1 to 2 months, but the pain returned. An exam a year later revealed a large amount of stage II cells in the right and left pelvic sidewalls, which were again treated with electrocautery. The patient continued treatment. A hysterectomy was performed, but the patient continued to have pain and again electrocauterization was done for adhesions on the sigmoid colon to the left pelvic wall. The patient had fever and nausea after this procedure. She returned to the hospital for surgical exploration of the abdomen during which a perforated colon and peritonitis were found. She had a colon resection and a complicated recovery, spending 5 days in the intensive care unit. She continues to have ongoing gastrointestina l problems and has permanent abdominal scarring. The patient sued her gynecologist and claimed he perforated her colon in the procedure for lysis of adhesions. The physician denied any negligence in performing the procedure, but a $250,000 verdict was returned against him. 24 magenta yellow cyan black CONTEMPORARYOBGYN.NET Neonatal care delayed during delivery AT 20 WEEKS’ GESTATION , a Virginia woman was referred for an ultrasound by her obstetrician, who suspected oomphalocele or gastroschisis. The scan revealed a gastroschisis with a moderate amount of bowel exposed. When the patient went to the hospital in labor at 38 weeks’ gestation, the fetal heart rate (FHR) tracing appeared to exhibit a somewhatsinusoidal pattern, and the physician who reviewed it described it as “almost” sinusoidal. The FHR subsequently accelerated to 60 bpm, and when the physician ruptured the membranes to place a scalp electrode, thick meconium was present. However, the pediatric service, nursery, and the neonatal intensive care unit (NICU) personnel were not notified of the meconium or gastroschisis at that time. The FHR continued erratically between 30 and 120 bpm, which was confirmed by placement of a second electrode. The infant then delivered precipitously. The Apgar scores were 2 at 1 minute, 2 at 5 minutes, and 4 at 10 minutes. The infant was nonresponsive, with meconium below the vocal cords, and the NICU team was called. When they arrived, t he i n fa nt showed no respiratory effort and his heart rate was 60 bpm. Suction and intubation attempted at 4 minutes of life were unsuccessful, and intubation was reattempted 1 minute l at e r. T h e i n i t i a l arterial blood gas showed severe metabolic acidosis. Gastroschisis ruled out infant cooling and the child experienced hypoxic-ischemic encephalopathy as a result of asphyxia. The child now has microcephaly, requires tube feeding, and will require lifetime care. Two lawsuits were fi led, one on behalf of the infant and one on behalf of the mother. The infant’s case was settled for $1.8 million; the mother’s case, for $1 million. The child now has microcephaly, requires tube feeding, and will require lifetime care. MS COLLINS is an attorney specializing in medical malpractice in Long Beach, California. She welcomes feedback on this column via e-mail to [email protected]. SEPTEMBER 2012 ES119667_obgyn0912_024.pgs 08.28.2012 11:41 ADV In cervical cancer screening, The devil is in the details The cobas® HPV Test helps you uncover disease that may be missed by cytology. The cobas® HPV test is the only clinically validated, FDA-approved assay that simultaneously provides pooled results on high-risk genotypes and individual results on the highest-risk genotypes HPV 16 and 18. The ATHENA study with more than 47,000 women showed that nearly 1 in 7 women, ≥30 years old, who tested positive for HPV 16, had high-grade cervical disease despite normal Pap results.1 Many professional health organizations 2-6 support co-testing with cytology and high-risk HPV testing for women 30 years and older. Order the cobas® HPV test to know more about patients at the highest risk of cervical cancer. Learn more at www.hpv16and18.com. ATHENA = Addressing THE Need for Advanced HPV Diagnostics; HPV = Human Papillomavirus 1. Wright T, et al. Am. J Clin. Pathol 2011; 136: 578–586. 2. American Cancer Society, 3. American Society for Colposcopy and Cervical Pathology (serial cytology remains an option for these women), 4. American Congress of Obstetrics and Gynecologists, 5. Institute of Medicine, 6. National Comprehensive Cancer Network © 2012 Roche Diagnostics. All rights reserved. COBAS is a trademark of Roche. ® The cobas HPV Test KNOW THE RISK magenta yellow cyan black ES111038_OBGYN0912_025_FP.pgs 08.20.2012 23:36 ADV GRAND ROUNDS Congenital diaphragmatic hernia Although relatively uncommon, CDH is a developmental delay that can result in severe neonatal complications and even death. Fortunately, antenatal ultrasound can help detect CDH, providing greater treatment options and outcomes for both patients and neonatals. BY anna K SFaKIanaKI, mD, mpH Dr SFaKIanaKI is associate professor of Maternal-Fetal Medicine at Yale University School of Medicine, New Haven, Connecticut. She reports that she has no conflicts of interest to disclose with regard to the content of this article. 26 magenta yellow cyan black c ongenital diaphragmatic hernia (CDH) is a developmental defect in the diaphragm during embryogenesis that allows the abdominal viscera to herniate into the chest cavity. It is not very common, but fortunately it can usually be detected with antenatal ultrasound (U/S). Te abdominal contents disrupt normal lung development, resulting in decreased bronchial branching, decreased alveolar number, decreased pulmonary vascularization, and overmuscularization of the pulmonary arterial tree.1 Ultimately, these findings can lead to pulmonary hypoplasia and pulmonary hypertension, which are the leading causes of death in a newborn. Incidence varies from 2.4 to 4.9 per 10,000.2 Neonatal outcomes are improved when delivery occurs in a tertiary care facility that specializes in CDH care, underscoring the importance of antenatal diagnosis.3 Most (75%) CDH occur in the left hemidiaphragm; 15% are right-sided; 10% contemporaryobgyn.net take-home messages ◾ When CDH is suspected, the patient should be referred for a detailed U/S and fetal echocardiogram. ◾ Improvements in antenatal imaging allow for early diagnosis of CDH. bilateral.4 However, in pregnancies complicated by fetal demise, 47% of CDH is lefsided; 27% is right-sided; and another 27% is bilateral.5 The pathogenesis of CDH is not completely understood but likely involves abnormal development of the diaphragm at 6 to 10 weeks’ gestation. Environmental exposures have been implicated, including periconceptional smoking, alcohol, vitamin A deficiency, thalidomide exposure, september 2012 ES120828_obgyn0912_026.pgs 08.30.2012 08:43 ADV CONGENITAL DIAGPHRAGMATIC HERNIA Congenital diaphragmatic hernia in the left hemidiaphragm and exposure to anticonvulsants. 6-9 Although most cases of CDH occur sporadically, familial cases have been described. Some single gene disorders are associated with CDH as well (Table 1).1,10 TABLe Major single-gene disorders associated with congenital diaphragmatic hernia Syndrome Inheritance gene Ultrasound findings beckwith-Wiedemann Autosomal dominant Autosomal dominant CDKNIC, NSD1 CDH7 Autosomal dominant, X-linked X-linked NIPBL, Smc1A Visceromegaly, abdominal wall defects, macroglossia Cardiac anomaly, coanal atresia, genitourinary anomalies, growth restriction, ear anomalies Characteristic facies, microencephaly, growth restriction, limb anomalies Craniosynostosis, hypertelorism CHArGe Ultrasound findings ILLUSTRATION BY MAYA SHOEMAKER, SHOEMAKER MEDICAL The major U/S finding with CDH is a mass in the thoracic cavity of varying echogenicity, accompanied by a mediastinal shift (Figure 1). The specific appearance will depend on what abdominal contents have herniated. In left-sided CDH, the f luid-filled fetal stomach tends to herniate, therefore, the thoracic mass appears cystic in nature. In these cases, the stomach is not visualized in its normal position within the abdomen (Figure 2). On sagittal imaging, the usual image of the stomach and heart on either side of the diaphragm cannot be obtained (Figure 3), and the cystic mass can be cephalad to the diaphragm (Figure 4). Because of mass effect, the heart often is displaced. The liver is herniated in approximately 50% of left-sided CDH, and that is an important prognostic indicator (Figure 5). Cornelia de Lange Craniofrontonasal dysplasia Donnai-barrow Autosomal recessive Fryns Unknown, Autosomal recessive Autosomal recessive matthew-Wood LRP2 Agenesis of the corpus callosum, omphalocele, hypertelorism Central nervous system, renal, and cardiac anomalies STRA6 micro- or anophthalmia, cardiac and genitourinary anomalies Hemivertebrae, fused vertebrae, rib anomalies multiple vertebral segmentation defects Autosomal recessive DLL3 simpson-Golabibehmel Denys-Drach/ Frasier/meacham X-linked GPC3 Autosomal dominant WT1 Overgrowth, limb, and renal anomalies Ambiguous genitalia, cryptophthalmos, renal anomalies Adapted from bianchi DW, et al1 and Holder Am, et al.10 september 2012 magenta yellow cyan black EFNB1 contemporary ob/gyn 27 ES120821_obgyn0912_027.pgs 08.30.2012 08:42 ADV CONGENITAL DIAGPHRAGMATIC HERNIA Figure 1 Transverse 4-Chamber View of 20-Week Fetus this scan demonstrates a large cystic mass in the thorax, with displacement of the heart to the right. the lung area to head circumference ratio was 1.27, which is in the range of intermediate prognosis. Figure 2 Absence of the Stomach Bubble on Transverse View In almost all cases of right-sided CDH, the liver herniates into the thoracic cavity. Because the liver and the lung have similar echogenicity, a discrete mass is not always visualized, and the diagnosis is suspect because of the mediastinal shif to the lef. Doppler imaging can highlight the vascular pattern of the liver within the thorax. Te gallbladder may also be seen within the thorax in right-sided CDH. Magnetic resonance imaging (MRI) may be useful for differentiating the liver from the remaining lung. Other U/S findings that may be associated with CDH include: • Abdominal circumference that lags behind the other biometry, and an abdomen that appears scaphoid; • Polyhydramnios, which is believed to occur because of compression of the esophagus; • Oligohydramnios in the setting of impaired fetal growth; • Depending on the size of the defect, change in position of the herniated contents over time; and • Peristalsis of herniated intestine on prolonged imaging, which may allow for differentiation from other thoracic masses. Increased nuchal translucency (NT) may be seen in the first trimester.11 Differential diagnoses this finding on U/S increases the likelihood of diagnosis of congenital diaphragmatic hernia. Figure 3 Two Parasagittal Images these images show the heart and stomach on either side of the diaphragm. that does not absolutely exclude congenital diaphragmatic hernia, because the herniated contents may shift from intrathoracic to intrabdominal positions if the defect is large enough. 28 magenta yellow cyan black contemporaryobgyn.net Major differential diagnoses include cystic lesions of the lung, specifically congenital cystic adenomatoid malformation, and bronchopulmonary sequestration. Tese can be differentiated from CDH by U/S findings. Other possible diagnoses include mediastinal teratomas, although they tend to be more vascular and the abdominal contents are in situ. Associated anomalies are found in approximately 40% to 60% of live-born infants with CDH, most commonly renal, gastrointestinal (GI), cardiac, and central nervous system anomalies.12,5 In 1 study, only 18% of anomalies were diagnosed antenatally, underscoring the importance of newborn evaluation.4 Te rate of associated anomalies is higher in cases of fetal demise, and additional anomalies are found in 95% of such cases.13 Chromosomal anomalies are found in 10% to 20% of cases of CDH, most commonly trisomies 21, 18, and 13.9 A syndromic etiology is found in 10% of cases (Table 1). september 2012 ES120820_obgyn0912_028.pgs 08.30.2012 08:42 ADV Deliver the Baby ... and the Post-Baby Body NON-SURGICAL • NON-INVASIVE Expand your Practice with the Best Choice in Body Shaping Lasers The latest in body contouring is now available: i-Lipo from Chromogenex, the worldwide leader in laser technology. i-Lipo uses low level laser energy to stimulate targeted areas into naturally releasing their stored fatty acids, shrinking fat cells, and reducing inches in those hard to tone areas. i-Lipo treatments are: • Safe — treat all skin types with no downtime • Fast — measurable results in 20 minute treatments • Pain Free — and no side effects BEFORE FDA Cleared Clinically Proven Outstanding ROI magenta yellow cyan black AFTER Grow your revenues while delivering the postpartum treatment your patients are looking for. For physician references, patient success stories, or to schedule an in-office demonstration, call 1-855-GET-ILIPO. www.ilipo.com/getyourbodyback ES119458_OBGYN0912_029_FP.pgs 08.28.2012 09:32 ADV CONGENITAL DIAGPHRAGMATIC HERNIA Figure 4 Antenatal evaluation Sagittal View of Cystic Mass a cystic mass is seen superior to the diaphragm at the level of the heart. the mass represents loops of fluid-filled intestine. Figure 5 Transverse View at 22 Weeks’ Gestation the heart is displaced to the right side of the chest whereas the left side is occupied by loops of bowel and the stomach. the lung-to-head ratio is 0.81, which reflects poor prognosis (<1.0). Figure 6 Imaging of Lung Area to Head Circumference Ratio the ratio was 1.27, which is in the range of intermediate prognosis. 30 magenta yellow cyan black contemporaryobgyn.net When CDH is suspected, the patient should be referred for a detailed U/S and fetal echocardiogram. Karyotype and consultation with a genetic counselor are suggested. Array comparative genomic hybridization can be considered. Consultation with a neonatologist and a pediatric surgeon should be arranged. Delivery should be planned at a tertiary care facility with extracorporeal membrane oxygenation (ECMO) capabilities. Termination of pregnancy can be considered when gestation is less than 24 weeks. Objective criteria for prediction of perinatal morbidity and mortality are important because they may not only influence decision for termination of pregnancy but also because eligibility for fetal therapy is predicated on poor prognosis. One of the most reliable factors is the presence or absence of liver herniation. In a systematic review that included 20 studies, survival rates were significantly lower in fetuses with liver herniation (45.4% vs 73.9%).14 Another widely used prognostic variable is lung-to-head circumference ratio (LHR). An axial image of the thorax is obtained at the level of the 4-chamber view, and the area of the lung contralateral to the defect is measured in 2 perpendicular planes.15 Te fetal head circumference is used to standardize the measurement (Figure 6). A cut-off of less than 1.0 has been suggested as poor prognosis and more than 1.6 as good prognosis in isolated, lef-sided CDH.16 However, a systematic review and metaanalysis of more than 20 studies found that LHR was not sensitive enough to use for discrimination between CDH survivors and nonsurvivors.15 This review was limited by the heterogeneity of the included studies. Because of the observation that the LHR increases exponentially during pregnancy, a modification was subsequently introduced.17 Referred to as the observed versus expected (o/e) LHR, it is expressed as a percentage of the expected LHR as calculated from a population of normal fetuses and has been correlated with both morbidity and mortality.18-20 Fetal lung volume is another prognostic variable that can be assessed either on 3-D U/S or via MRI but is still not validated enough to be used september 2012 ES120826_obgyn0912_030.pgs 08.30.2012 08:43 ADV The GEA Results Are In Patient Satisfaction NovaSure ThermaChoice NovaSure patients were 3x more likely to be satisfied with the procedure than ThermaChoice patients and over 9x more likely to be satisfied with the procedure than HTA patients HTA Achieving Amenorrhea NovaSure ThermaChoice HTA NovaSure patients were almost 5x more likely to achieve amenorrhea than ThermaChoice patients and 3x more likely to achieve amenorrhea than HTA patients All results are statistically significant. An independent meta-analysis, including 19 studies with over 3000 women, concluded that NovaSure was more effective than ThermaChoice and HTA in the treatment of heavy menstrual bleeding. Daniels, et al. Second generation endometrial ablation techniques for heavy menstrual bleeding: network meta-anlysis. BMJ. 2012 April [Epub ahead of print] ADS-00746-001 Rev. 001 magenta yellow cyan black ES119469_OBGYN0912_031_FP.pgs 08.28.2012 09:33 ADV CONGENITAL DIAGPHRAGMATIC HERNIA clinically. A recent systematic review found that both total fetal lung volume (TFLV) and o/e TLFV were significantly higher in survivors, irrespective of the side of the defect.21 Limitations of MRI include fetal positioning, fetal movement, maternal comfort, and cost. Antenatal monitoring Monitoring afer initial evaluation will depend on the severity of the lesion and the associated anomalies. In the absence of significant associated anomalies or aneuploidy, the most important prognostic signs are liver herniation, right-sided lesion, and attenuated FLV. Te size of the actual defect cannot be assessed antenatally, and these markers serve as a surrogate.20 Monitoring consists of serial U/S to assess for fetal growth. The amniotic fluid volume is reassessed at each visit. Antenatal testing is usually initiated at about 32 to 33 weeks and consists of weekly to twice-weekly modified biophysical profile evaluation. In the case of abnormal testing, especially after 34 weeks, delivery should be strongly considered. Antenatal corticosteroids are administered before 34 weeks if a preterm delivery is anticipated; steroids administered after 34 weeks have not been associated with improved outcomes. 3 When growth is adequate and testing is normal, most centers time delivery so that the appropriate consultants are available, including the team prepared for ECMO. Cesarean delivery is reserved for the usual obstetric indications. 22,23 In utero therapy As a rule, in utero therapy has been reserved for cases with the worst prognosis based on risk of pulmonary hypoplasia. Te first attempts at repair involved patching the actual diaphragmatic defect; however, results were poor.24 Subsequently, therapy has been aimed at reversing the processes that lead to pulmonary hypoplasia, namely, compression of the lungs. In vitro and animal models suggested that tracheal occlusion could improve pulmonary development by obstructing the outflow of pulmonary fluids, leading to lung expansion. Unfortunately, clinical trials have had mixed outcomes. The first studies used an open approach via hysterotomy; outcomes were poor, with survival 32 magenta yellow cyan black contemporaryobgyn.net rates of less than 35%. 25,26 Thereafter, an endoscopic approach was developed to advance a balloon into the fetal trachea. A trial was initiated to examine the role of fetal endoscopic tracheal occlusion (FETO) in isolated CDH with poor prognosis defined by liver herniation and an LHR of less than 1.4. 27 This trial was stopped before completion because of a high rate of prematurity coupled with no survival benefit in the treated patients (73%), largely because of an unexpected high survival rate in the control group (77%). However, the study has been criticized for using the LHR cut off of 1.4, which led to inclusion of less severely affected fetuses. Te European “FETO Consortium” conducted a single-arm, multicenter study in severe CDH, defined by liver herniation and LHR of less than 1. 28 The balloon is placed at 26 to 28 weeks and reversed at 34 weeks. Rates of preterm premature rupture of membranes (47.1%) and preterm delivery (30.9%) were both high. However, survival was increased over what was predicted, and the procedure is being offered in European centers. A number of ongoing trials are examining FETO. Tracheal occlusion is not being performed in the United States outside of these trials. Neonatal management Infants with CDH usually present with respiratory distress that is reflective of the degree of pulmonary hypoplasia. Endotracheal intubation and pressor support are usually required. Extracorporeal membrane oxygenation is frequently used for respiratory failure, although the literature is inconclusive about its effect on survival. 29 Pulmonary hypertension is ofen seen and may require therapy with vasodilators. Management ultimately involves reducing the herniated viscera and surgically repairing the diaphragmatic defect. In the past, immediate repair was the norm, but now most researchers agree that it should be delayed until a newborn is clinically stable. 30 Traditionally, repair has been done via an open surgical approach, using either a patch repair or a muscle flap. Minimally invasive techniques have been introduced but may be associated with a higher rate of hernia recurrence. 31 Complications afer repair include recurrent hernia, gastroesophageal ref lux disease, failure to thrive, and patch related complications. september 2012 ES120825_obgyn0912_032.pgs 08.30.2012 08:42 ADV For your OAB patients with urge urinary incontinence Any moment is an accident waiting to happen. TOVIAZ provides powerful efficacy.1,2 Median % reduction from baseline in UUI episodes at Week 12 Mean UUI episodes per 24 hours at baseline Mean UUI episodes per 24 hours at Week 12 Placebo TOVIAZ 4 mg TOVIAZ 8 mg 3.7 3.8 3.7 (n=211) (n=199) (n=223) -50% -80%* 2.5 1.8* -88%* 1.4* *P≤0.001 vs placebo.1 Results of a 12-week, fixed-dose, randomized, double-blind, placebo- and active-controlled international ex-US study to assess the efficacy, tolerability, and safety of TOVIAZ in adults with overactive bladder. The coprimary efficacy end points were change in micturitions per day and change in UUI episodes per day. Subjects (N=1132) were treated once daily with placebo, TOVIAZ 4 mg or 8 mg, or an active-control agent (an oral antimuscarinic). The median percent change in micturitions at Week 12 was 19% for TOVIAZ 8 mg, 17% for TOVIAZ 4 mg, and 11% for placebo (P<0.001). The least squares (LS) mean change in micturitions at Week 12 was -1.9 episodes for TOVIAZ 8 mg, -1.8 episodes for TOVIAZ 4 mg, and -1.0 episodes for placebo (P<0.001). The median percent reduction in UUI episodes at Week 12 was 88% for TOVIAZ 8 mg, 80% for TOVIAZ 4 mg, and 50% for placebo (P≤0.001). The LS mean change in UUI episodes at Week 12 was -2.2 episodes for TOVIAZ 8 mg, -2.0 episodes for TOVIAZ 4 mg, and -1.1 episodes for placebo (P≤0.001).1 TOVIAZ is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. Important Safety Information TOVIAZ is contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma, and in patients with known hypersensitivity to the drug or its ingredients or to DETROL® (tolterodine tartrate) tablets or DETROL® LA (tolterodine tartrate extended release capsules). Angioedema of the face, lips, tongue, and/or larynx has been reported with fesoterodine, in some cases after the first dose. Patients should be advised to promptly discontinue fesoterodine therapy and seek immediate medical attention if they experience edema of the tongue, laryngopharynx, or difficult breathing. TOVIAZ tablets should be used with caution in patients with clinically significant bladder outlet obstruction, decreased gastrointestinal motility, controlled narrow-angle glaucoma, or myasthenia gravis. The recommended starting dose of TOVIAZ is 4 mg once daily swallowed whole. Based upon individual response and tolerability, the dose may be increased to 8 mg once daily. Doses greater than 4 mg are not recommended in patients with severe renal insufficiency (CLCR <30 mL/min), or in patients taking a potent CYP3A4 inhibitor. TOVIAZ is not recommended for use in patients with severe hepatic impairment (Child-Pugh C). The most frequently reported adverse events (≥4%) for TOVIAZ were: dry mouth (placebo, 7%; TOVIAZ 4 mg, 19%; TOVIAZ 8 mg, 35%) and constipation (placebo, 2%; TOVIAZ 4 mg, 4%; TOVIAZ 8 mg, 6%). OAB=overactive bladder. References: 1. Chapple C, Van Kerrebroeck P, Tubaro A, et al. Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder. Eur Urol. 2007;52(4):1204-1212. 2. Data on file. Protocol SP583 table SCS763 13.2.1.1.1. Pfizer Inc, New York, NY. For more information, visit www.ToviazHCP.com. Please see brief summary of prescribing information on next page. FSD01158A/FSD432612 magenta yellow cyan black © 2012 Pfizer Inc. All rights reserved. February 2012 ES111039_OBGYN0912_033_FP.pgs 08.20.2012 23:36 ADV TOVIAZ® (fesoterodine fumarate) extended release tablets Rx only BRIEF SUMMARY OF PRESCRIBING INFORMATION. The following is a brief summary only; see full Prescribing Information for complete product information. INDICATIONS AND USAGE Toviaz is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. CONTRAINDICATIONS Toviaz is contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Toviaz is also contraindicated in patients with known hypersensitivity to the drug or its ingredients, or to tolterodine tartrate tablets or tolterodine tartrate extended-release capsules. WARNINGS AND PRECAUTIONS Angioedema: Angioedema of the face, lips, tongue, and/or larynx has been reported with fesoterodine. In some cases angioedema occurred after the first dose. Angioedema associated with upper airway swelling may be life-threatening. If involvement of the tongue, hypopharynx, or larynx occurs, fesoterodine should be promptly discontinued and appropriate therapy and/or measures to ensure a patent airway should be promptly provided. Bladder Outlet Obstruction: Toviaz should be administered with caution to patients with clinically significant bladder outlet obstruction because of the risk of urinary retention. Decreased Gastrointestinal Motility: Toviaz, like other antimuscarinic drugs, should be used with caution in patients with decreased gastrointestinal motility, such as those with severe constipation. Controlled Narrow-Angle Glaucoma: Toviaz should be used with caution in patients being treated for narrow-angle glaucoma, and only where the potential benefits outweigh the risks. Hepatic Impairment: Toviaz has not been studied in patients with severe hepatic impairment and therefore is not recommended for use in this patient population. Renal Impairment: Doses of Toviaz greater than 4 mg are not recommended in patients with severe renal impairment. Concomitant Administration with CYP3A4 Inhibitors: Doses of Toviaz greater than 4 mg are not recommended in patients taking a potent CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, clarithromycin). No dosing adjustments are recommended in the presence of moderate CYP3A4 inhibitors (eg, erythromycin, fluconazole, diltiazem, verapamil and grapefruit juice). While the effect of weak CYP3A4 inhibitors (eg, cimetidine) was not examined by clinical study, some pharmacokinetic interaction is expected, albeit less than that observed with moderate CYP3A4 inhibitors. Myasthenia Gravis: Toviaz should be used with caution in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction. ADVERSE REACTIONS Clinical Trials Experience: The safety of Toviaz was evaluated in Phase 2 and 3 controlled trials in a total of 2859 patients with overactive bladder, of which 2288 were treated with fesoterodine. Of this total, 782 received Toviaz 4 mg/day, and 785 received Toviaz 8 mg/day in Phase 2 or 3 studies with treatment periods of 8 or 12 weeks. Approximately 80% of these patients had >10 weeks exposure to Toviaz in these trials. A total of 1964 patients participated in two 12-week, Phase 3 efficacy and safety studies and subsequent open-label extension studies. In these two studies combined, 554 patients received Toviaz 4 mg/day and 566 patients received Toviaz 8 mg/day. In Phase 2 and 3 placebo-controlled trials combined, the incidences of serious adverse events in patients receiving placebo, Toviaz 4 mg, and Toviaz 8 mg were 1.9%, 3.5%, and 2.9%, respectively. All serious adverse events were judged to be not related or unlikely to be related to study medication by the investigator, except for four patients receiving Toviaz who reported one serious adverse event each: angina, chest pain, gastroenteritis, and QT prolongation on ECG. The most commonly reported adverse event in patients treated with Toviaz was dry mouth. The incidence of dry mouth was higher in those taking 8 mg/day (35%) and in those taking 4 mg/day (19%), as compared to placebo (7%). Dry mouth led to discontinuation in 0.4%, 0.4%, and 0.8% of patients receiving placebo, Toviaz 4 mg, and Toviaz 8 mg, respectively. For those patients who reported dry mouth, most had their first occurrence of the event within the first month of treatment. The second most commonly reported adverse event was constipation. The incidence of constipation was 2% in those taking placebo, 4% in those taking 4 mg/day, and 6% in those taking 8 mg/day. Table 1 lists adverse events, regardless of causality, that were reported in the combined Phase 3, randomized, placebo-controlled trials at an incidence greater than placebo and in 1% or more of patients treated with Toviaz 4 or 8 mg once daily for up to 12 weeks. Table 1. Adverse events with an incidence exceeding the placebo rate and reported by ≥1% of patients from double-blind, placebo-controlled Phase 3 trials of 12 weeks treatment duration Placebo N=554 % Toviaz 4 mg/day N=554 % Toviaz 8 mg/day N=566 % Dry mouth 7.0 18.8 34.6 Constipation 2.0 4.2 6.0 Dyspepsia 0.5 1.6 2.3 Nausea 1.3 0.7 1.9 Abdominal pain upper 0.5 1.1 0.5 Urinary tract infection 3.1 3.2 4.2 Upper respiratory tract infection 2.2 2.5 1.8 System organ class Gastrointestinal disorders Infections Preferred term Eye disorders Dry eyes 0 1.4 3.7 Renal and urinary disorders Dysuria 0.7 1.3 1.6 Urinary retention 0.2 1.1 1.4 Respiratory disorders Cough 0.5 1.6 0.9 Dry throat 0.4 0.9 2.3 General disorders Edema peripheral 0.7 0.7 1.2 Musculoskeletal disorders Back pain 0.4 2.0 0.9 Psychiatric disorders Insomnia 0.5 1.3 0.4 Investigations ALT increased 0.9 0.5 1.2 GGT increased 0.4 0.4 1.2 Rash 0.5 0.7 1.1 Skin disorders ALT = alanine aminotransferase; GGT = gamma glutamyltransferase Patients also received Toviaz for up to three years in open-label extension phases of one Phase 2 and two Phase 3 controlled trials. In all open-label trials combined, 857, 701, 529, and 105 patients received Toviaz for at least 6 months, 1 year, 2 years, and 3 years, respectively. The adverse events observed during long-term, open-label studies were similar to those observed in the 12-week, placebo-controlled studies, and included dry mouth, constipation, dry eyes, dyspepsia, and abdominal pain. Similar to the controlled studies, most adverse events of dry mouth and constipation were mild to moderate in intensity. Serious adverse events, judged to be at least possibly related to study medication by the investigator and reported more than once during the open-label treatment period of up to 3 years, included urinary retention (3 cases), diverticulitis (3 black cases), constipation (2 cases), irritable bowel syndrome (2 cases), and electrocardiogram QT corrected interval prolongation (2 cases). Post-marketing Experience: The following events have been reported in association with fesoterodine use in worldwide post-marketing experience: Eye disorders: Blurred vision; Cardiac disorders: Palpitations; General disorders and administrative site conditions: hypersensitivity reactions, including angioedema with airway obstruction, face edema; Skin and subcutaneous tissue disorders: Urticaria, pruritus. Because these spontaneously reported events are from the worldwide post-marketing experience, the frequency of events and the role of fesoterodine in their causation cannot be reliably determined. DRUG INTERACTIONS Antimuscarinic Drugs: Coadministration of Toviaz with other antimuscarinic agents that produce dry mouth, constipation, urinary retention, and other anticholinergic pharmacological effects may increase the frequency and/or severity of such effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. CYP3A4 Inhibitors: Doses of Toviaz greater than 4 mg are not recommended in patients taking potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, and clarithromycin. Coadministration of the potent CYP3A4 inhibitor ketoconazole with fesoterodine led to approximately a doubling of the maximum concentration (Cmax ) and area under the concentration versus time curve (AUC) of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine. Compared with CYP2D6 extensive metabolizers not taking ketoconazole, further increases in the exposure to 5-HMT were observed in subjects who were CYP2D6 poor metabolizers taking ketoconazole. There is no clinically relevant effect of moderate CYP3A4 inhibitors on the pharmacokinetics of fesoterodine. Following blockade of CYP3A4 by coadministration of the moderate CYP3A4 inhibitor fluconazole 200 mg twice a day for 2 days, the average (90% confidence interval) increase in Cmax and AUC of the active metabolite of fesoterodine was approximately 19% (11%-28%) and 27% (18%-36%) respectively. No dosing adjustments are recommended in the presence of moderate CYP3A4 inhibitors (eg, erythromycin, fluconazole, diltiazem, verapamil and grapefruit juice). The effect of weak CYP3A4 inhibitors (eg, cimetidine) was not examined; it is not expected to be in excess of the effect of moderate inhibitors. CYP3A4 Inducers: No dosing adjustments are recommended in the presence of CYP3A4 inducers, such as rifampin and carbamazepine. Following induction of CYP3A4 by coadministration of rifampin 600 mg once a day, Cmax and AUC of the active metabolite of fesoterodine decreased by approximately 70% and 75%, respectively, after oral administration of Toviaz 8 mg. The terminal half-life of the active metabolite was not changed. CYP2D6 Inhibitors: The interaction with CYP2D6 inhibitors was not tested clinically. In poor metabolizers for CYP2D6, representing a maximum CYP2D6 inhibition, Cmax and AUC of the active metabolite are increased 1.7- and 2-fold, respectively. No dosing adjustments are recommended in the presence of CYP2D6 inhibitors. Drugs Metabolized by Cytochrome P450: In vitro data indicate that at therapeutic concentrations, the active metabolite of fesoterodine does not have the potential to inhibit or induce Cytochrome P450 enzyme systems. Oral Contraceptives: In the presence of fesoterodine, there are no clinically significant changes in the plasma concentrations of combined oral contraceptives containing ethinyl estradiol and levonorgestrel. Warfarin: A clinical study has shown that fesoterodine 8 mg once daily has no significant effect on the pharmacokinetics or the anticoagulant activity (PT/INR) of warfarin 25 mg. Standard therapeutic monitoring for warfarin should be continued. Drug-Laboratory Test Interactions: Interactions between Toviaz and laboratory tests have not been studied. USE IN SPECIFIC POPULATIONS Pregnancy: Pregnancy Category C. There are no adequate and well-controlled studies using Toviaz in pregnant women. No dose-related teratogenicity was observed in reproduction studies performed in mice and rabbits. In mice at 6 to 27 times the expected exposure at the maximum recommended human dose (MRHD) of 8 mg based on AUC (75 mg/kg/day, oral), increased resorptions and decreased live fetuses were observed. One fetus with cleft palate was observed at each dose (15, 45, and 75 mg/kg/day), at an incidence within the background historical range. In rabbits treated at 3 to 11 times the MRHD (27 mg/kg/day, oral), incompletely ossified sternebrae (retardation of bone development) were observed in fetuses. In rabbits at 9 to 11 times the MRHD (4.5 mg/kg/day, subcutaneous), maternal toxicity and incompletely ossified sternebrae were observed in fetuses (at an incidence within the background historical range). In rabbits at 3 times the MRHD (1.5 mg/kg/ day, subcutaneous), decreased maternal food consumption in the absence of any fetal effects was observed. Oral administration of 30 mg/kg/day fesoterodine to mice in a pre- and post-natal development study resulted in decreased body weight of the dams and delayed ear opening of the pups. No effects were noted on mating and reproduction of the F1 dams or on the F2 offspring. Toviaz should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. Nursing Mothers: It is not known whether fesoterodine is excreted in human milk. Toviaz should not be administered during nursing unless the potential benefit outweighs the potential risk to the neonate. Pediatric Use: The pharmacokinetics of fesoterodine have not been evaluated in pediatric patients.The safety and effectiveness of Toviaz in pediatric patients have not been established. Geriatric Use: No dose adjustment is recommended for the elderly. The pharmacokinetics of fesoterodine are not significantly influenced by age. Of 1567 patients who received Toviaz 4 mg/day or 8 mg/day in the Phase 2 and 3, placebo-controlled, efficacy and safety studies, 515 (33%) were 65 years of age or older, and 140 (9%) were 75 years of age or older. No overall differences in safety or effectiveness were observed between patients younger than 65 years of age and those 65 years of age or older in these studies; however, the incidence of antimuscarinic adverse events, including dry mouth, constipation, dyspepsia, increase in residual urine, dizziness (at 8 mg only) and urinary tract infection, was higher in patients 75 years of age and older as compared to younger patients. Renal Impairment: In patients with severe renal impairment (CLCR <30 mL/min), Cmax and AUC are increased 2.0- and 2.3-fold, respectively. Doses of Toviaz greater than 4 mg are not recommended in patients with severe renal impairment. In patients with mild or moderate renal impairment (CLCR ranging from 30-80 mL/min), Cmax and AUC of the active metabolite are increased up to 1.5- and 1.8-fold respectively, as compared to healthy subjects. No dose adjustment is recommended in patients with mild or moderate renal impairment. Hepatic Impairment: Patients with severe hepatic impairment (Child-Pugh C) have not been studied; therefore Toviaz is not recommended for use in these patients. In patients with moderate (Child-Pugh B) hepatic impairment, Cmax and AUC of the active metabolite are increased 1.4- and 2.1-fold, respectively, as compared to healthy subjects. No dose adjustment is recommended in patients with mild or moderate hepatic impairment. Gender: No dose adjustment is recommended based on gender. The pharmacokinetics of fesoterodine are not significantly influenced by gender. Race: Available data indicate that there are no differences in the pharmacokinetics of fesoterodine between Caucasian and Black healthy subjects following administration of Toviaz. OVERDOSAGE Overdosage with Toviaz can result in severe anticholinergic effects. Treatment should be symptomatic and supportive. In the event of overdosage, ECG monitoring is recommended. Manufactured by: Aesica Pharmaceuticals GmbH, Galileistraße 6, 08056 Zwickau, Germany Distributed by: Pfizer Labs, Division of Pfizer Inc, NY, NY 10017 LAB-0381-10.0 Revised November 2011 FSD01151A/FSD423505-01 © 2011 Pfizer Inc. All rights reserved. December 2011 ES110992_OBGYN0912_034_FP.pgs 08.20.2012 23:33 ADV CONGENITAL DIAGPHRAGMATIC HERNIA Prognosis Spontaneous intrauterine fetal demise occurs in 2% to 4% of cases. 32 Of fetuses who survive to delivery, the survival rate with isolated CDH is reportedly 60% to 80%. 21 Prognosis is worse in right-sided lesions and in the setting of liver herniation, both of which are associated with a survival rate of less than 45%. Survival rates of 0% to 15% have been reported in fetuses with an o/e LHR of 0% to 15%, and most experts would recommend in utero therapy. Survival rates of 60% to 75% are expected in fetuses with an o/e LHR of 25% to 45% and in utero therapy in this group is controversial. Fetuses with an o/e LHR of more than 45% are very likely to survive and can be monitored expectantly. 33 A systematic review of controlled trials showed that neonatal survival was improved in infants diagnosed prenatally and those born at a tertiary care facility.3 Mortality was higher in the presence of additional anomalies, iatrogenic lung injury, severe pulmonary hypoplasia, and persistent pulmonary hypertension. Infants transported after delivery to a tertiary care facility use more ECMO than inborn infants and have a higher mortality rate afer surgery.34 As is the case in other aspects of obstetrics, major disparities occur on the basis of race and socioeconomic status. In a study of 2,774 neonatal intensive-care unit hospitalizations, blacks experienced 50% excess mortality compared with those of white race. 35 In another study, black race was associated with lower survival rates and greater use of ECMO.36 The most common long-term complications involve the pulmonary, musculoskeletal, GI, and neurodevelopmental systems and can be seen in 20% to 30% of patients.1 Pulmonary complications include need for bronchodilator therapy and obstructive airway disease. Musculoskeletal complications include deformities such as pectus excavatum and scoliosis. 37 Neurodevelopmental outcomes include delays in fine and gross motor skills, visuospatial skills, cognition and behavioral skills, and speech and language skills. 38 Factors that correlate with immediate neonatal outcome, such as liver herniation, also seem to correlate with long-term outcome. 39 Recurrence risk for nonsyndromic CDH is reported at less than 2%.12 Recurrence in the setting of complex CDH would depend on the exact diagnosis, and consultation with a genetic counselor would be useful. SUMMARY CDH is a developmental delay that can result in severe neonatal complications and even death. Improvements in antenatal imaging allow for early diagnosis of CDH, and thorough evaluation for associated anomalies and syndromes, enabling patients to choose termination of pregnancy if they desire. For patients who choose to continue the pregnancy, early detection allows for transfer to a tertiary care facility with the proper resources to optimize outcome. RefeRences 1. 1. Bianchi DW, Crombleholme TM, D’Alton ME, Malone FE. Fetology. Diagnosis and Management of the Fetal Patient. 2nd ed. New York: McGraw Hill; 2010;278-291. 2. Wright JC, Budd JL, Field DJ, Draper ES. Epidemiology and outcome of congenital diaphragmatic hernia: a 9-year experience. Paediatr Perinat Epidemiol. 2011;25(2):144-149. 3. Logan JW, Rice HE, Goldberg RN, Cotten CM. Congenital diaphragmatic hernia: a systematic review and summary of bestevidence practice strategies. J Perinatol. 2007;27(9):535-549. 4. Zaiss I, Kehl S, Link K, et al. Associated malformations in congenital diaphragmatic hernia. Am J Perinatol. 2011;28(3):211-218. 5. Brownlee EM, Howatson AG, Davis CF, Sabharwal AJ. The hidden mortality of congenital diaphragmatic hernia: a 20-year review. J Pediatr Surg. 2009;44(2):317-320. 6. Caspers KM, Oltean C, Romitti PA, et al; National Birth Defects Prevention Study. Maternal periconceptional exposure to cigarette smoking and alcohol consumption and congenital diaphragmatic hernia. Birth Defects Res A Clin Mol Teratol. 2010;88(12):1040-1049. 7. Felix JF, van Dooren MF, Klaassens M, Hop WC, Torfs CP, Tibboel D. Environmental factors in the etiology of esophageal atresia and congenital diaphragmatic hernia: results of a case-control study. Birth Defects Res A Clin Mol Teratol. 2008;82(2):98-105. 8. Yang W, Shaw GM, Carmichael SL, et al; National Birth Defects Prevention Study. Nutrient intakes in women and congenital diaphragmatic hernia in their offspring. Birth Defects Res A Clin Mol Teratol. 2008;82(3):131-138. 9. Enns GM, Cox VA, Goldstein RB, Gibbs DL, Harrison MR, Golabi M. Congenital diaphragmatic defects and associated syndromes, malformations, and chromosome anomalies: a retrospective study of 60 patients and literature review. Am J Med Genet. 1998;79:215-225. september 2012 magenta yellow cyan black contemporary ob/gyn 35 ES120824_obgyn0912_035.pgs 08.30.2012 08:42 ADV CONGENITAL DIAGPHRAGMATIC HERNIA 10. Holder AM, Klaassens M, Tibboel D, de Klein A, Lee B, Scott DA. Genetic factors in congenital diaphragmatic hernia. Am J Hum Genet. 2007;80(5):825-845. 24. Harrison MR, Adzick NS, Bullard KM, et al. Correction of congenital diaphragmatic hernia in utero VII: a prospective trial. J Pediatr Surg. 1997;32(11):1637-1642. 11. Sebire NJ, Snijders RJ, Davenport M, Greenough A, Nicolaides KH. Fetal nuchal translucency thickness at 10-14 weeks’ gestation and congenital diaphragmatic hernia. Obstet Gynecol. 1997;90(6):943-946. 25. Harrison MR, Adzick NS, Flake AW, et al. Correction of congenital diaphragmatic hernia in utero VIII: response of the hypoplastic lung to tracheal occlusion. J Pediatr Surg. 1996;31(10):1339-1348. 12. Skari H, Bjornland K, Haugen G, Egeland T, Emblem R. Congenital diaphragmatic hernia: a meta-analysis of mortality factors. J Pediatr Surg. 2000;35(8):1187-1197. 26. Flake AW, Crombleholme TM, Johnson MP, Howell LJ, Adzick NS. Treatment of severe congenital diaphragmatic hernia by fetal tracheal occlusion: clinical experience with fifteen cases. Am J Obstet Gynecol. 2000;183(5):1059-1066. 13. Puri P, Gorman F. Lethal nonpulmonary anomalies associated with congenital diaphragmatic hernia: implications for early intrauterine surgery. J Pediatr Surg. 1984;19(1):29-32. 14. Mullassery D, Ba’ath ME, Jesudason EC, Losty PD. Value of liver herniation in prediction of outcome in fetal congenital diaphragmatic hernia: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2010;35(5):609-614. 15. Ba’ath ME, Jesudason EC, Losty PD. How useful is the lungto-head ratio in predicting outcome in the fetus with congenital diaphragmatic hernia? A systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2007;30(6):897-906. 16. Jani J, Keller RL, Benachi A, et al; Antenatal-CDHRegistry Group. Prenatal prediction of survival in isolated left-sided diaphragmatic hernia. Ultrasound Obstet Gynecol. 2006;27(1):18-22. 17. Peralta CF, Cavoretto P, Csapo B, Vandecruys H, Nicolaides KH. Assessment of lung area in normal fetuses at 12-32 weeks. Ultrasound Obstet Gynecol. 2005;26(7):718-724. 18. Jani JC, Benachi A, Nicolaides KH, et al; Antenatal-CDHRegistry Group. Prenatal prediction of neonatal morbidity in survivors with congenital diaphragmatic hernia: a multicenter study. Ultrasound Obstet Gynecol. 2009;33(1):64-69. 19. Jani J, Nicolaides KH, Keller RL, et al; Antenatal-CDH-Registry Group. Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol. 2007;30(1):67-71. 29. Mugford M, Elbourne D, Field D. Extracorporeal membrane oxygenation for severe respiratory failure in newborn infants. Cochrane Database Syst Rev. 2008;(3):CD001340. 30. Moyer V, Moya F, Tibboel R, Losty P, Nagaya M, Lally KP. Late versus early surgical correction for congenital diaphragmatic hernia in newborn infants. Cochrane Database Syst Rev. 2002;(3):CD001695. 31. Tsao K, Lally PA, Lally KP; Congenital Diaphragmatic Hernia Study Group. Minimally invasive repair of congenital diaphragmatic hernia. J Pediatr Surg. 2011;46(6):1158-1164. 32. Gallot D, Boda C, Ughetto S, et al. Prenatal detection and outcome of congenital diaphragmatic hernia: a French registry-based study. Ultrasound Obstet Gynecol. 2007;29(3):276-283. 33. Gucciardo L, Deprest J, Done’ E, et al. Prediction of outcome in isolated congenital diaphragmatic hernia and its consequences for fetal therapy. Best Pract Res Clin Obstet Gynaecol. 2008;22(1):123-138. 34. Aly H, Bianco-Batlles D, Mohamed MA, Hammad TA. Mortality in infants with congenital diaphragmatic hernia: a study of the United States National Database. J Perinatol. 2010;30(8):553-557. 35. Sola JE, Bronson SN, Cheung MC, Ordonez B, Neville HL, Koniaris LG. Survival disparities in newborns with congenital diaphragmatic hernia: a national perspective. J Pediatr Surg. 2010;45(6):1336-1342. 21. Mayer S, Klaritsch P, Petersen S, et al. The correlation between lung volume and liver herniation measurements by fetal MRI in isolated congenital diaphragmatic hernia: a systematic review and meta-analysis of observational studies. Prenat Diagn. 2011;31(11):1086-1096. 36. Stevens TP, van Wijngaarden E, Ackerman KG, Lally PA, Lally KP; Congenital Diaphragmatic Hernia Study Group. Timing of delivery and survival rates for infants with prenatal diagnoses of congenital diaphragmatic hernia. Pediatrics. 2009;123(2):494-502. 37. Nobuhara KK, Lund DP, Mitchell J, Kharasch V, Wilson JM. Longterm outlook for survivors of congenital diaphragmatic hernia. Clin Perinatol. 1996;23(4):873-887. 23. Safavi A, Lin Y, Skarsgard ED; Canadian Pediatric Surgery Network. Perinatal management of congenital diaphragmatic hernia: when and how should babies be delivered? Results from the Canadian Pediatric Surgery Network. J Pediatr Surg. 2010;45(12):2334-2339. black 28. Jani JC, Nicolaides KH, Gratacós E, et al. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol. 2009;34(3):304-310. 20. Alfaraj MA, Shah PS, Bohn D, et al. Congenital diaphragmatic hernia: lung-to-head ratio and lung volume for prediction of outcome. Am J Obstet Gynecol. 2011;205(1):43e1-43.e8. 22. Frenckner BP, Lally PA, Hintz SR, Lally KP; Congenital Diaphragmatic Hernia Study Group. Prenatal diagnosis of congenital diaphragmatic hernia: how should the babies be delivered? J Pediatr Surg. 2007;42(9):1533-1538. 36 27. Harrison MR, Keller RL, Hawgood SB, et al. A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med. 2003;349(20):1916-1924. contemporaryobgyn.net 38. Danzer E, Hedrick HL. Neurodevelopmental and neurofunctional outcomes in children with congenital diaphragmatic hernia. Early Hum Dev. 2011;87(9):625-632. 39. Danzer E, Gerdes M, Bernbaum J, et al. Neurodevelopmental outcome of infants with congenital diaphragmatic hernia prospectively enrolled in an interdisciplinary follow-up program. J Pediatr Surg. 2010;45(9):1759-1766. september 2012 ES120823_obgyn0912_036.pgs 08.30.2012 08:42 ADV Colposcopy for Electronic Medical Records TriStar with digital USB video camera TriStar with digital camera Wallach provides many options for digital colposcopy with zoom and multi-step magnification colposcopes. Choose from digital 35mm camera or USB video camera. All colposcopes now come with Trulight LED lighting, for whiter, brighter light. Choose the premier Wallach overhead suspension arm; imitations don’t hold up to the rugged, durable design. Center post colposcope stands are also available. Please call us at 800.243.2463 to arrange for a product demonstration. Nothing works like a WA L L AC H S U R G I C A L D E V I C E S P H O N E 2 0 3 . 7 9 9 . 2 0 0 0 | magenta yellow cyan black • 7 5 CO R P O R AT E D R I V E • T R U M B U L L , C T 0 6 6 1 1 U S A FAX 2 0 3 . 7 9 9 . 2 0 0 2 • W W W. WA L L AC H S U R G I C A L . CO M ES110989_OBGYN0912_037_FP.pgs 08.20.2012 23:33 ADV SURGICAL WOUNDS Surgical Wounds Strategies for Minimizing Complications Wound infection and wound separation are relatively common in the obstetric population. The keys to reducing the occurrence and severity of these complications are optimization of host risk factors, preoperative preparation, surgical technique, and wound management. BY JaSon KnIgHt, mD, anD peDro F. eScobar, mD Dr. KnIgHt is a fellow at the Cleveland Clinic Foundation, Division of Gynecologic Oncology. Dr. eScobar is a staff physician in the Department of Obstetrics/ Gynecology and Women’s Institute at the Cleveland Clinic and the Director of Laparoscopy and Robotic Surgery. He is also an Associate Professor of Surgery for the Cleveland Clinic Lerner College of Medicine of Case Western University in Cleveland, Ohio. Neither author has a conflict to disclose with repect to the contents of this article. 38 magenta yellow cyan black W ound infection and suprafascial wound separation are common events that result in readmission in 1% of women who undergo cesarean delivery. 1 Wound infection complicates 1.5% to 3.8% of cesarean deliveries, whereas suprafascial wound separation complicates 3.6% of cesarean deliveries 1-3 In patients undergoing abdominal hysterectomy, incidence of wound infection is as high as 11%, whereas approximately 2% have suprafascial wound separation.4,5 Fascial dehiscence is rare, complicating 0.4% of total abdominal hysterectomies. 6 In several series, it was not observed afer obstetric or gynecologic procedures in which a Pfannensteil incision was used.7,8 Risk of wound infection is lower with a laparoscopic approach than with abdominal hysterectomy (OR 0.31; 95% CI 0.12-0.77), with the largest series demonstrating a wound infection rates of 3% versus 22%, respectively.9,10 In a systematic review, incidence of trocar site hernia was estimated to be 0.5%.11 Factors associated with wound complications can be categorized as host-related or unrelated. Host-related risk factors include comorbidities such as diabetes, obesity, poor nutritional status, and smoking. Factors contemporaryobgyn.net take-home message ◾ Wound complications are common in surgical patients but several strategies can aid in prevention and treatment. unrelated to the host typically involve the perioperative environment: adequacy of skin preparation, preoperative antibiotics, and postoperative wound care. Tis article discusses how optimizing these factors, to the extent possible, will increase the likelihood of uneventful wound healing. Host factors Poorly controlled diabetes mellitus (DM), obesity, malnutrition, smoking, and immune compromise have all been demonstrated to be independent risk factors for wound complications.12 Wound complications— and most notably infection and wound breakdown—are more common in obese patients and 2-fold more prevalent in those with DM.13 Tight glycemic control during the perioperative period is associated with decreased incidence of wound complications.14 Hyperglycemia is associated with decreased september 2012 ES119842_obgyn0912_038.pgs 08.28.2012 13:21 ADV SURGICAL WOUNDS cytokine expression and delayed re-epithelialization, conditions that conceivably increase wound infection risk.15 Te independent association between obesity and increased risk of wound complications is more difficult to explain. Nonetheless, among obstetric and gynecologic patients, increasing thickness of subcutaneous tissue is associated with increased risk of wound infection.4,16 Smoking is a risk factor for wound infection, with an odds ratio of 1.2 (CI 1.14-1.32).17 It has been shown to decrease oxygen tension within the wound bed, a putative mechanism for the observed association between smoking and SSI.18 Malnutrition is ofen encountered in patients with advanced gynecologic malignancy but rarely in women undergoing benign obstetric and gynecologic procedures. Serum albumin levels are a reliable marker of nutritional status, and perioperative hypoalbuminemia is associated with increased incidence of wound complications and perioperative morbidity.19 Nutrition therapy to facilitate wound healing should be considered for patients who cannot tolerate oral nutrition within 7 days of surgery.20 Pregnancy is not considered a risk factor for wound complications, but it is worth acknowledging that its attendant hormonal milieu may impact the body’s response to surgical wounds. Both estrogen and progesterone impact wound healing. Estrogen inhibits macrophage inhibiting factor (MIF), a potent pro-inflammatory protein. In mice, hypoestrogenism with overexpression of MIF results in excessive wound inflammation and poor wound healing.21 Te role of progestins in wound healing is less clear. Progesterone has been associated with cytokine response to injury, and in one mouse study, progesterone supplementation improved wound healing in castrated female mice.22 Serum cortisol levels more than double by 26 weeks’ gestation.23 Chronic steroid use in humans and pulsed steroid administration in mice are associated with increased wound failure rates.24,25 Studies in rats demonstrate that wounds occurring during pregnancy heal with less tensile strength than those in non-pregnant rats.26 Whether these observations suggest a clinically significant difference in wound healing during pregnancy in humans has yet to be determined. Well-controlled comparisons of surgical wound morbidity in pregnant versus nonpregnant women are lacking, but data derived from 183 laparoscopic appendectomies performed during pregnancy revealed no hernias and only one wound infection.27 Non-host factors A distinction should be made between surgical-site contamination as a result of bacteria residing on the skin and contamination of typically sterile compartments (such as the intraperitoneal cavity) and that from entry into organs with contents that are often or always unsterile (such as the POWER POINTS colon or vagina during colpotomy). Control Choice of incision, of these distinct types of contamination difparticularly in fers, as described below. Surface microbes obese patients, are managed with surgical-site preparation, impacts the likelihood whereas intraluminal microbes are manof wound aged with prophylactic systemic antibiotics complications. administered based upon the likelihood of disseminating intraluminal pathogens. Skin preparation Preoperative skin cleansing has received much attention in recent years. In addition to performing standard surgical-site preparation in the operating room, many centers now advise patients to take an antiseptic bath at home the day before surgery. Antiseptic bathing before surgery has been shown to decrease the skin microbial load and is recommended by the Centers for Disease Control and Prevention (CDC), but randomized prospective trials have failed to demonstrate that the practice significantly decreases surgical-site infections (SSIs).28 A Cochrane review of 10,000 surgical patients demonstrated equivalent SSI rates regardless of randomization to preoperative antiseptic bathing versus a control group.29 Some authors theorize that preoperative antiseptic bathing does not decrease incidence of wound complications because much of the chlorhexidine tends to be rinsed away by patients. A new approach is use of chlorhexidine-impregnated washcloths both the night before and the morning of surgery, with no rinse afterward. So far, only limited, nonrandomized data are available about this practice.30 Surgical-site preparation in the operating room is an important preoperative decontamination procedure and researchers have attempted to identify the most effective method. Darouiche et al compared 30-day wound infection rates in patients undergoing clean-contaminated procedures who were randomized to either chlorhexidine-alcohol scrub or povidone-iodine scrub at the time of surgery.31 In that study, both superficial (4.2% vs 8.6%; P=.008) and deep (1% vs 3%; P=.05) incisional infections were september 2012 magenta yellow cyan black Superficial wound infection may resolve with debridement and improved wound care, but antibiotic therapy is indicated for deep wound infections. contemporary ob/gyn 39 ES119840_obgyn0912_039.pgs 08.28.2012 13:21 ADV SURGICAL WOUNDS less common in patients prepped with chlorhexidinealcohol than with povidone-iodine. preoperative antibiotics Preoperative antibiotic prophylaxis has been shown to reduce postoperative infections in appropriately selected patients.32 Need for prophylactic preoperative antibiotics is determined by risk of wound infection, based upon the degree of expected wound contamination. Te CDC advocates surgical wound classification to preoperatively gauge risk of surgical site infection based on expected contamination (Table 1).28 Tis classification predicts risk of wound infection and provides the rationale for antibiotic prophylaxis before surgery.33 Antibiotic prophylaxis is indicated for Class II to IV wounds and for select patients with Class I wounds for whom infection poses “catastrophic risk” or who are receiving prosthetic implants.28 When antibiotics are indicated, drug choice is determined based on the typical pathogens expected with the planned procedure.34 Te Joint Commission’s Surgical Care Improvement Project (SCIP) provides guidelines for selecting appropriate prophylactic antibiotics for hysterectomy which should be administered within 1 hour of incision (Table 2). ACOG recommendations are concordant with SCIP. In addition, ACOG recommends antibiotic prophylaxis for urogynecology procedures.35 Diagnostic laparoscopy, exploratory laparotomy, hysteroscopy (operative or diagnostic), endometrial biopsy and IUD placement do not require antibiotics. ACOG recommends doxycyclin prophylasis for induced or surgical abortion and for hysterosalpingograms if the patient has a history of PID or the study reveals tubal dilation.35 Prophylactic antibiotics TABLE 1 Surgical wound classification28 classification 40 magenta yellow cyan black type of wound infection Wound infection risk without prophylaxis Class I Clean Uninfected wounds without operative entry into the GI or GU systems, primarily closed Class II CleanContaminated Wounds with operative entry into the GI or GU systems, but without gross contamination <30% Class III Contaminated major breach of sterile field, gross spillage of GI contents or incision through inflamed nonpurulent tissue <60% Class IV Dirty/Infected Incision through or into existing infection >60% contemporaryobgyn.net 2% at the time of cesarean delivery reduce the incidence of wound complications.36 A recent meta-analysis of prospective, randomized studies demonstrated that administering antibiotics before incision instead of after cord clamping decreases maternal morbidity without adverse neonatal effects.37 ACOG recommends a single dose of a first generation cephalosporin prior to incision. Among penicillin allergic patients, clindamycin plus an aminoglycoside are a reasonable alternative. Single dose vancomycin can be added to prophylaxis among patients known to be colonized by methicillin-resistant Staphylococcus aureus (MRSA).38 Surgical considerations Data are limited on the association between surgical technique and wound outcomes, but basic surgical principles believed to contribute to favorable wound healing include: achievement of hemostasis while minimizing tissue trauma;28 maintenance of the integrity of the sterile field;39,40 avoidance of unnecessarily long anesthesia time;41 and avoidance of intraoperative hypothermia, which is associated with increased risk of wound infection and postoperative morbidity.42 Choice of incision, particularly in obese patients, impacts the likelihood of wound complications. Vertical incision carries an odds ratio of complications (defined as infection and suprafascial wound separation) of 10.7 compared with a Pfannenstiel incision.2 While incision selection is ofen determined by the type of exposure required to safely perform the planned procedure, where possible, use of a Pfannenstiel incision may confer an advantage, in terms of wound integrity, compared with a vertical incision. The theoretical advantage of placing a subcutaneous drain during surgery is to prevent seroma or hematoma formation, which can lead to wound separation and infection. Randomized controlled trials of prophylactic drain placement at the time of cesarean delivery have produced equivocal results. A recent meta-analysis of exiting data suggested that drain placement does not improve wound outcomes.43 Although skin closure with staples is faster than subcuticular stitching, individual randomized studies in obstetrics have been equivocal about wound outcomes. However, a recent meta-analysis of 5 prospective, randomized controlled trials suggested that closure with sutures is superior to staples as measured by the incidence of wound separation and infection.44 Closure with surgical adhesive has not been rigorously studied in obstetrics and gynecology, but randomized data from general surgery suggest that staples september 2012 ES120144_obgyn0912_040.pgs 08.29.2012 07:58 ADV BUILDING CALCIUM COMPLIANCE ® CITRACAL Slow Release 1200 A once-daily calcium supplement • Slo-Cal™ Technology releases calcium continuously for efficient absorption • 1200 mg of calcium plus 1000 IU of Vitamin D3 in 2 tablets (one serving) RECOMMEND CITRACAL Slow Release Scan this QR code with your smartphone to order CITRACAL samples for your patients. Visit our healthcare professional Web site at www.citracalpro.com. © 2012 Bayer HealthCare LLC magenta yellow cyan black July 2012 47114-6333 BUILT FOR COMPLIANCE ES110987_OBGYN0912_041_FP.pgs 08.20.2012 23:33 ADV SURGICAL WOUNDS and adhesive afford similar cosmesis and wound integrity.45 managing wound infections Despite adequate perioperative care, wound infection and wound separation still occur. Signs and symptoms of wound infection include erythema, induration, pain, tenderness, suppurative discharge, wound odor, and wound separation. Clinical criteria have been established for diagnosis of wound infection. The National Nosocomial Infection Surveillance System (NNIS), a project of the CDC, has established clinical guidelines for diagnosis of surgical site infection.46 According to these guidelines, surgical site infection is classified as either superficial or deep and must occur within 30 days of surgery. Superficial infections involve the skin or subcutaneous tissue, and diagnosis requires one of the following: purulent drainage, a positive wound culture, symptoms of infection accompanied by deliberate opening of the wound (except when wound culture returns negative) or diagnosis made by the attending physician. Deep infections involve the fascial or muscle layer and diagnosis requires one of the following: deep purulent drainage that is not coming from an organ space, spontaneous dehiscence (or deliberate, if accompanied by fever >38°C or symptoms, except when wound culture returns negative), discovery of abscess in the deep tissue or when diagnosed by the attending. Application of standardized criteria has been validated, and in one study, use of the criteria resulted in diagnostic concordance with wound culture in 97% of cases.47 The approach to the infected wound should include remova l of a sufficient number TABLE 2 Antibiotics for of staples or sutures preoperative prophylaxis around the infected in hysterectomy patients area to allow assessment cefotetan, cefazolin, cefoxitin, of the subcutaneous cefuroxime, ampicillin/sulbactam or tissues and fascia.48 Te ertapenem fascia should be probed If β-lactam allergic: to assess its integrity. Clindamycin + aminoglycoside OR Subcutaneous tissue Clindamycin + quinolone should be examined and OR irrigated and devitalized Clindamycin + aztreonam areas debrided. In most OR metronidazole + aminoglycoside cases, debridement of OR small wounds can be metronidazole + quinolone achieved at the bedside Adapted from Joint Commission, surgical Care af ter appropriate Improvement project, 2012 42 magenta yellow cyan black contemporaryobgyn.net analgesia. Operative debridement may be required for large wounds, and in such cases, consultation with a wound care team is reasonable. Superficial wound infection may resolve with debridement and improved wound care, but antibiotic therapy is indicated for deep wound infections.48,49 Unless directed by wound cultures or unique patient circumstances, antibiotic therapy should be targeted against the expected pathogens as determined by surveillance data. Te NNIS has identified gram-negative bacilli, enterococci, Group B strep, and anaerobes as the most common pathogens found in surgical site infections afer obstetric and gynecologic surgery.34 Te Infectious Disease Society of America (IDSA) has offered guidelines regarding initiation and choice of antibiotics in the setting of surgical site infections after abdominal surgery.49 Opening of the wound and close observation is adequate for patients without tachycardia and temperature <38.5°C. For patients with wound infection and tachycardia or fever at or above 38.5°C, the IDSA recommends cefotetan or ampicillin/sulbactam. A fluoroquinolone plus clindamycin is an acceptable alternative for nonpregnant patients afer gynecologic surgery. Antibiotic selection to cover MRSA should be considered for patients at risk of MRSA infection, including those who reside in nursing facilities, have a prolonged hospital admission, or are colonized by MRSA. caring for the separated wound Adequate wound care is required for the separated wound or wounds opened by the clinician to manage infection or seroma. In this setting, clinical experience supports the concept that moisture facilitates wound healing by providing a medium for migration of lymphocytes, macrophages, and fibroblasts.50 Categorizing a wound in terms of size, need for debridement, and moisture level may be helpful in selecting dressing material that adequately covers the wound while providing a moist environment without trapping excessive drainage.51 A multitude of wound care products exist and can be categorized by their ability to retain moisture as occlusive, semi-occlusive, absorptive, or open. Occlusive dressings allow diffusion of relatively small amounts of moisture. Examples include films such as Tegaderm and colloids such as DuoDerm and Aquacel. Whereas Tegaderm is simply a vaporpermeable film, hydrocolloids interact with the wound exudate and become a gel, preventing exudate dispersion and keeping a wound moist. september 2012 ES119898_obgyn0912_042.pgs 08.28.2012 14:13 ADV LYSTEDA CAN HELP ® • LYSTEDA cannot induce clot formation because it acts downstream from coagulation* • Efficacy seen as soon as her next period and every period thereafter • Studied long-term in a 27-cycle study across a range of patients *If a patient were to have a spontaneous thrombus independent of LYSTEDA, the breakdown of that thrombus could potentially be slowed by LYSTEDA. LYSTEDA is contraindicated in women with active thromboembolic disease or a history or intrinsic risk of thrombosis or thromboembolism, including retinal vein or artery occlusion; or known hypersensitivity to tranexamic acid. LYSTEDA® (tranexamic acid) tablets are indicated for the treatment of cyclic heavy menstrual bleeding. Prior to prescribing LYSTEDA, exclude endometrial pathology that can be associated with heavy menstrual bleeding. Important Safety Information The risk of thrombotic and thromboembolic events may increase further when hormonal contraceptives are administered with LYSTEDA, especially in women who are obese or smoke cigarettes. Women using hormonal contraception should use LYSTEDA only if there is a strong medical need and the benefit of treatment will outweigh the potential increased risk of a thrombotic event. Do not use LYSTEDA in women who are taking more than the approved dose of a hormonal contraceptive. Concomitant use of LYSTEDA with Factor IX complex concentrates, anti-inhibitor coagulant concentrates or all-trans retinoic acid (oral tretinoin) may increase risk of thrombosis. Visual or ocular adverse effects may occur with LYSTEDA. Immediately discontinue use if visual or ocular symptoms occur. In case of severe allergic reaction, discontinue LYSTEDA and seek immediate medical attention. Cerebral edema and cerebral infarction may be caused by use of LYSTEDA in women with subarachnoid hemorrhage. Ligneous conjunctivitis has been reported in patients taking tranexamic acid. The most common adverse reactions in clinical trials (≥5%, and more frequent in LYSTEDA subjects compared to placebo subjects) were: headache, sinus and nasal symptoms, back pain, abdominal pain, musculoskeletal pain, joint pain, muscle cramps, migraine, anemia, and fatigue. LYSTEDA has not been studied in adolescents under age 18 with heavy menstrual bleeding. For more information and valuable patient offers, please visit www.LYSTEDA.com. Please see Brief Summary of Prescribing Information on following page. For full Prescribing Information, please visit www.lysteda.com ©2012 Ferring Pharmaceuticals Inc. magenta yellow cyan black Lysteda.com 04/12 LYS_CONOB_001_0412 ES110986_OBGYN0912_043_FP.pgs 08.20.2012 23:33 ADV LYSTEDA® (tranexamic acid) tablets BRIEF SUMMARY OF PRESCRIBING INFORMATION Please consult package insert for full Prescribing Information INDICATIONS AND USAGE LYSTEDA® (tranexamic acid) Tablets is indicated for the treatment of cyclic heavy menstrual bleeding. Prior to prescribing LYSTEDA, exclude endometrial pathology that can be associated with heavy menstrual bleeding. CONTRAINDICATIONS Thromboembolic Risk: Do not prescribe LYSTEDA to women who are known to have the following conditions: active thromboembolic disease (e.g., deep vein thrombosis, pulmonary embolism, or cerebral thrombosis); a history of thrombosis or thromboembolism, including retinal vein or artery occlusion; an intrinsic risk of thrombosis or thromboembolism (e.g., thrombogenic valvular disease, thrombogenic cardiac rhythm disease, or hypercoagulopathy). Venous and arterial thrombosis or thromboembolism, as well as cases of retinal artery and retinal vein occlusions, have been reported with tranexamic acid. Hypersensitivity to Tranexamic Acid: Do not prescribe LYSTEDA to women with known hypersensitivity to tranexamic acid [see Warnings and Precautions and Adverse Reactions]. WARNINGS AND PRECAUTIONS Thromboembolic Risk: Concomitant Use of Hormonal Contraceptives: Combination hormonal contraceptives are known to increase the risk of venous thromboembolism, as well as arterial thromboses such as stroke and myocardial infarction. Because LYSTEDA is antifibrinolytic, the risk of venous thromboembolism, as well as arterial thromboses such as stroke, may increase further when hormonal contraceptives are administered with LYSTEDA. This is of particular concern in women who are obese or smoke cigarettes, especially smokers over 35 years of age [see Contraindications and Drug Interactions]. Women using hormonal contraception were excluded from the clinical trials supporting the safety and efficacy of LYSTEDA, and there are no clinical trial data on the risk of thrombotic events with the concomitant use of LYSTEDA with hormonal contraceptives. There have been US postmarketing reports of venous and arterial thrombotic events in women who have used LYSTEDA concomitantly with combined hormonal contraceptives. Women using hormonal contraception, especially those who are obese or smoke, should use LYSTEDA only if there is a strong medical need and the benefit of treatment will outweigh the potential increased risk of a thrombotic event. Do not use LYSTEDA in women who are taking more than the approved dose of a hormonal contraceptive. Factor IX Complex Concentrates or Anti-Inhibitor Coagulant Concentrates: LYSTEDA is not recommended for women taking either Factor IX complex concentrates or anti-inhibitor coagulant concentrates because the risk of thrombosis may be increased [see Drug Interactions]. All-Trans Retinoic Acid (Oral Tretinoin): Exercise caution when prescribing LYSTEDA to women with acute promyelocytic leukemia taking all-trans retinoic acid for remission induction because of possible exacerbation of the procoagulant effect of all-trans retinoic acid [see Drug Interactions]. Ocular Effects: Retinal venous and arterial occlusion has been reported in patients using tranexamic acid. Patients should be instructed to report visual and ocular symptoms promptly. In the event of such symptoms, patients should be instructed to discontinue LYSTEDA immediately and should be referred to an ophthalmologist for a complete ophthalmic evaluation, including dilated retinal examination, to exclude the possibility of retinal venous or arterial occlusion. Severe Allergic Reaction: A case of severe allergic reaction to LYSTEDA was reported in the clinical trials, involving a subject who experienced dyspnea, tightening of her throat, and facial flushing that required emergency medical treatment. A case of anaphylactic shock has also been reported in the literature, involving a patient who received an intravenous bolus of tranexamic acid. Subarachnoid Hemorrhage: Cerebral edema and cerebral infarction may be caused by use of LYSTEDA in women with subarachnoid hemorrhage. Ligneous Conjunctivitis: Ligneous conjunctivitis has been reported in patients taking tranexamic acid. The conjunctivitis resolved following cessation of the drug. ADVERSE REACTIONS Clinical Trial Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Short-term Studies: The safety of LYSTEDA in the treatment of heavy menstrual bleeding (HMB) was studied in two randomized, double-blind, placebo-controlled studies. One study compared the effects of two doses of LYSTEDA (1950 mg and 3900 mg given daily for up to 5 days during each menstrual period) versus placebo over a 3-cycle treatment duration. A total of 304 women were randomized to this study, with 115 receiving at least one dose of 3900 mg/day of LYSTEDA. A second study compared the effects of LYSTEDA (3900 mg/day) versus placebo over a 6-cycle treatment duration. A total of 196 women were randomized to this study, with 117 receiving at least one dose of LYSTEDA. In both studies, subjects were generally healthy women who had menstrual blood loss of ≥80 mL. In these studies, subjects were 18 to 49 years of age with a mean age of approximately 40 years, had cyclic menses every 21-35 days, and a BMI of approximately 32 kg/m2. On average, subjects had a history of HMB for approximately 10 years and 40% had fibroids as determined by transvaginal ultrasound. Approximately 70% were Caucasian, 25% were Black, and 5% were Asian, Native American, Pacific Islander, or Other. Seven percent (7%) of all subjects were of Hispanic origin. Women using hormonal contraception were excluded from the trials. The rates of discontinuation due to adverse events during the two clinical trials were comparable between LYSTEDA and placebo. In the 3-cycle study, the rate in the 3900 mg LYSTEDA dose group was 0.8% as compared to 1.4% in the placebo group. In the 6-cycle study, the rate in the LYSTEDA group was 2.4% as compared to 4.1% in the placebo group. Across the studies, the combined exposure to 3900 mg/day LYSTEDA was 947 cycles and the average duration of use was 3.4 days per cycle. The following adverse events occurred in ≥5% of subjects and more frequently in LYSTEDA-treated subjects receiving 3900 mg/day (N=232) compared to placebo (N=139). The total number of adverse events reported with LYSTEDA was 1500 versus 923 with placebo. The number of subjects with at least one adverse event was 208 (89.7%) with LYSTEDA versus 122 (87.8%) with placebo. The following adverse events reported in LYSTEDA-treated subjects receiving 3900 mg/day and placebo, respectively, were (n/%): headache (includes headache and tension headache): 117 (50.4%), 65 (46.8%); nasal & sinus symptoms (includes nasal, respiratory tract and sinus congestion, sinusitis, acute sinusitis, sinus headache, allergic sinusitis and sinus pain, and multiple allergies and seasonal allergies): 59 (25.4%), 24 (17.3%); back pain: 48 (20.7%), 21 (15.1%); abdominal pain (includes abdominal tenderness and discomfort): 46 (19.8%), 25 (18.0%); musculoskeletal pain (includes musculoskeletal discomfort and myalgia): 26 (11.2%), 4 (2.9%); arthralgia (includes joint stiffness and swelling): 16 (6.9%), 7 (5.0%); muscle cramps & spasms: 15 (6.5%), 8 (5.8%); migraine: 14 (6.0%), 8 (5.8%); anemia: 13 (5.6%), 5 (3.6%); and fatigue: 12 (5.2%), 6 (4.3%). Long-term Studies: Long-term safety of LYSTEDA was studied in two open-label studies. In one study, subjects with physician-diagnosed heavy menstrual bleeding (not using the alkaline hematin methodology) were treated with 3900 mg/day for up to 5 days during each menstrual period for up to 27 menstrual cycles. A total of 781 subjects were enrolled and 239 completed the study through 27 menstrual cycles. A total of 12.4% of the subjects withdrew due to adverse events. Women using hormonal contraception were excluded from the study. The total exposure in this study to 3900 mg/day LYSTEDA was 10,213 cycles. The average duration of LYSTEDA use was 2.9 days per cycle. A long-term open-label extension study of subjects from the two short-term efficacy studies was also conducted in which subjects were treated with 3900 mg/day for up to 5 days during each menstrual period for up to 9 menstrual cycles. A total of 288 subjects were enrolled and 196 subjects completed the study ©2012 Ferring Pharmaceuticals Inc. black 04/12 through 9 menstrual cycles. A total of 2.1% of the subjects withdrew due to adverse events. The total exposure to 3900 mg/day LYSTEDA in this study was 1,956 cycles. The average duration of LYSTEDA use was 3.5 days per cycle. The types and severity of adverse events in these two long-term open-label trials were similar to those observed in the double-blind, placebo-controlled studies although the percentage of subjects reporting them was greater in the 27-month study, most likely because of the longer study duration. A case of severe allergic reaction to LYSTEDA was reported in the extension trial, involving a subject on her fourth cycle of treatment, who experienced dyspnea, tightening of her throat, and facial flushing that required emergency medical treatment. Postmarketing Experience: The following adverse reactions have been identified from postmarketing experience with tranexamic acid. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Based on US and worldwide postmarketing reports, the following have been reported in patients receiving tranexamic acid for various indications: nausea, vomiting, and diarrhea, allergic skin reactions, anaphylactic shock and anaphylactoid reactions, thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, cerebral thrombosis, acute renal cortical necrosis, and central retinal artery and vein obstruction), impaired color vision and other visual disturbances, dizziness. DRUG INTERACTIONS No drug-drug interaction studies were conducted with LYSTEDA. Hormonal Contraceptives: Because LYSTEDA is antifibrinolytic, concomitant use of hormonal contraception and LYSTEDA may further exacerbate the increased thrombotic risk associated with combination hormonal contraceptives. Women using hormonal contraception should use LYSTEDA only if there is a strong medical need and the benefit of treatment will outweigh the potential increased risk of a thrombotic event [see Warnings and Precautions]. Tissue Plasminogen Activators: Concomitant therapy with tissue plasminogen activators may decrease the efficacy of both LYSTEDA and tissue plasminogen activators. Therefore, exercise caution if a woman taking LYSTEDA therapy requires tissue plasminogen activators. Factor IX Complex Concentrates or Anti-Inhibitor Coagulant Concentrates: LYSTEDA is not recommended for women taking either Factor IX complex concentrates or anti-inhibitor coagulant concentrates because the risk of thrombosis may be increased [see Warnings and Precautions]. All-Trans Retinoic Acid (Oral Tretinoin): Exercise caution when prescribing LYSTEDA to women with acute promyelocytic leukemia taking all-trans retinoic acid for remission induction because of possible exacerbation of the procoagulant effect of all-trans retinoic acid [see Warnings and Precautions]. USE IN SPECIFIC POPULATIONS Pregnancy (Category B): LYSTEDA is not indicated for use in pregnant women. Reproduction studies have been performed in mice, rats and rabbits and have revealed no evidence of impaired fertility or harm to the fetus due to tranexamic acid. However, tranexamic acid is known to cross the placenta and appears in cord blood at concentrations approximately equal to the maternal concentration. There are no adequate and well-controlled studies in pregnant women. An embryo-fetal developmental toxicity study in rats and a perinatal developmental toxicity study in rats were conducted using tranexamic acid. No adverse effects were observed in either study at doses up to 4 times the recommended human oral dose of 3900 mg/day based on mg/m2 (actual animal dose 1500 mg/kg/day). Nursing Mothers: Tranexamic acid is present in the mother’s milk at a concentration of about one hundredth of the corresponding serum concentration. LYSTEDA should be used during lactation only if clearly needed. Pediatric Use: LYSTEDA is indicated for women of reproductive age and is not intended for use in premenarcheal girls. LYSTEDA has not been studied in adolescents under age 18 with heavy menstrual bleeding. Geriatric Use: LYSTEDA is indicated for women of reproductive age and is not intended for use by postmenopausal women. Renal Impairment: The effect of renal impairment on the pharmacokinetics of LYSTEDA has not been studied. Because tranexamic acid is primarily eliminated via the kidneys by glomerular filtration with more than 95% excreted as unchanged in urine, dosage adjustment in patient with renal impairment is needed. Hepatic Impairment: The effect of hepatic impairment on the pharmacokinetics of LYSTEDA has not been studied. Because only a small fraction of the drug is metabolized, dosage adjustment in patients with hepatic impairment is not needed. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenesis: Carcinogenicity studies with tranexamic acid in male mice at doses as high as 6 times the recommended human dose of 3900 mg/day showed an increased incidence of leukemia which may have been related to treatment. Female mice were not included in this experiment. The dose multiple referenced above is based on body surface area (mg/m2). Actual daily dose in mice was up to 5000 mg/kg/day in food. Hyperplasia of the biliary tract and cholangioma and adenocarcinoma of the intrahepatic biliary system have been reported in one strain of rats after dietary administration of doses exceeding the maximum tolerated dose for 22 months. Hyperplastic, but not neoplastic, lesions were reported at lower doses. Subsequent long-term dietary administration studies in a different strain of rat, each with an exposure level equal to the maximum level employed in the earlier experiment, have failed to show such hyperplastic/neoplastic changes in the liver. Mutagenesis: Tranexamic acid was neither mutagenic nor clastogenic in the in vitro Bacterial Reverse Mutation Assay (Ames test), in vitro chromosome aberration test in Chinese hamster cells, and in in vivo chromosome aberration tests in mice and rats. Impairment of Fertility: Reproductive studies performed in mice, rats and rabbits have not revealed any evidence of impaired fertility or adverse effects on the fetus due to tranexamic acid. In a rat embryo-fetal developmental toxicity study, tranexamic acid had no adverse effects on embryo-fetal development when administered during the period of organogenesis (from gestation days 6 through 17) at doses 1, 2 and 4 times the recommended human oral dose of 3900 mg/day. In a perinatal-postnatal study in rats, tranexamic acid had no adverse effects on pup viability, growth or development when administered from gestation day 6 through postnatal day 20 at doses 1, 2 and 4 times the recommended human oral dose of 3900 mg/day. The dose multiples referenced above are based on body surface area (mg/m2). Actual daily doses in rats were 300, 750 or 1500 mg/kg/day. Animal Toxicology and/or Pharmacology: Ocular Effects: In a 9-month toxicology study, dogs were administered tranexamic acid in food at doses of 0, 200, 600, or 1200 mg/kg/day. These doses are approximately 2, 5, and 6 times, respectively, the recommended human oral dose of 3900 mg/day based on AUC. At 6 times the human dose, some dogs developed reversible reddening and gelatinous discharge from the eyes. Ophthalmologic examination revealed reversible changes in the nictitating membrane/conjunctiva. In some female dogs, the presence of inflammatory exudate over the bulbar conjunctival mucosa was observed. Histopathological examinations did not reveal any retinal alteration. No adverse effects were observed at 5 times the human dose. In other studies, focal areas of retinal degeneration were observed in cats, dogs and rats following oral or intravenous tranexamic acid doses at 6-40 times the recommended usual human dose based on mg/m2 (actual animal doses between 250-1600 mg/kg/day). Rx only This summary provides important information about LYSTEDA. For full prescribing information, please visit www.Lysteda.com. LYS_CONOB_001_0412 ES110960_OBGYN0912_044_FP.pgs 08.20.2012 23:32 ADV SURGICAL WOUNDS Semiocclusive dressings include Adaptic (silicone gauze) and Xeroform (petrolatum gauze). These dressings allow exudates to pass through and are best used with an absorptive wet-to-dry cover dressing. Semi-occlusive dressings are useful for moist wounds. They have the added advantage of not sticking to wounds and can be used underneath packing material in deep wounds to protect granulation tissue and reduce discomfort associated with dressing removal. Alginates, such as Curasorb, are derived from seaweed, highly absorptive, and useful for controlling exudates from wet wounds. Care should be taken to change dressings on wet wounds frequently to prevent infection of absorbed exudates. Alginates ofen are packaged as ribbon or pads that can be applied to a wound bed. Afer absorbing fluid, the alginate becomes a gel that can be wiped or irrigated away at the time of dressing changes. Alginates are best used with a cover dressing and because they are absorptive, care should be taken to prevent excessive wound drying. Plain gauze bandage is considered an open dressing. Its primary advantage is ready availability. Among its limitations is the tendency to stick to wound beds, which may disrupt granulation tissue. Gauze is somewhat absorptive but not well suited for highly exudative wounds. Without an occlusive cover dressing, gauze is not optimal for retaining moisture in dry wounds. Terefore, it is best used in combination with other products to minimize adherence to the wound bed and improve moisture control. free of infection and gross contamination.57 It is still a reasonable option for selected patients, but wound closure is achieved with VAC in most cases.58 Prospective randomized trials comparing outcomes between secondary wound closure and VAC are lacking. closure of deep or large wounds RefeRences For small, shallow wounds in easily accessible locations, conservative management using the previously mentioned dressings and packing is usually sufficient. Patients with deep, large wounds—particularly those that are poorly accessible, such as under the pannus or in the vulva of morbidly obese patients—are at risk of both complicated and protracted wound healing.52 For such patients, packing and frequent dressing changes are impractical. Vacuum-assisted closure (VAC) can be helpful in this setting, but data from randomized controlled comparisons of VAC and traditional wound care are lacking.53,54 Theoretical advantages of VAC include less frequent dressing changes (typically every 3 days), consistent moisture control, reduced bacterial load, increased blood flow, and enhanced wound granulation compared to conventional wound care.55,56 Before widespread use of VAC, secondary closure was common and accepted once a wound was found to have healthy granulation tissue on all surfaces and 1. Ferres MA, Olivarez SA, Trinh V, Davidson C, Sangi-Haghpeykar H, Aagaard-Tillery KM. Rate of wound complications with enoxaparin use among women at high risk for postpartum thrombosis. Obstet Gynecol. 2011;117(1):119-124. 2. Thornburg LL, Linder MA, Durie DE, Walker B, Pressman EK, Glantz JC. Risk factors for wound complications in morbidly obese women undergoing primary cesarean delivery. J. Matern Fetal Neonatal Med. (2012). 3. Edwards JR, Peterson KD, Mu Y et al. National Healthcare Safety Network (NHSN) report: data summary for 2006 through 2008, issued December 2009. Am J Infect Control. 2009;37(10):783-805. 4. Soper DE, Bump RC, Hurt WG. Wound infection after abdominal hysterectomy: effect of the depth of subcutaneous tissue. Am J Obstet Gynecol. 1995;173(2):465-9; discussion 469-71. 5. Hemsell DL, Hemsell PG, Nobles B, Johnson ER, Little BB, Heard M. Abdominal wound problems after hysterectomy with electrocautery vs. scalpel subcutaneous incision. Infect Dis Obstet Gynecol. 1(1), 27-31 (1993). 6. Conde-Agudelo A. Intrafascial abdominal hysterectomy: outcomes and complications of 867 operations. Int J Gynaecol Obstet. 2000;68(3):233-239. 7. Mowat J, Bonnar J. Abdominal wound dehiscence after caesarean section. Br Med J. 1971;2(5756):256-257. 8. Orr JW, Jr, Orr PJ, Bolen DD, Holimon JL. Radical hysterectomy: does the type of incision matter? Am J Obstet Gynecol. 1995;173(2):399-405; discussion 405-406. 9. Nieboer TE, Johnson N, Lethaby A, et al. Surgical approach to hysterectomy for benign gynaecological disease. Cochrane Database Summary Ob/gyns should be aware that wound complications are common in surgical patients but that several strategies can aid in prevention and treatment. Laparoscopic surgery is associated with a lower incidence of wound infection as compared to open surgery. Obesity, diabetes, smoking, and malnutrition are among host risk factors for wound complications. In diabetic patients, glucose control is crucial before, during, and afer surgery to facilitate wound healing. Proper skin preparation, appropriate use of preoperative antibiotics, minimizing intraoperative contamination and attention to surgical technique are important steps to minimize wound complications. Wound infections involving subcutaneous tissues require opening, debridement, proper wound care and antibiotics in the setting of fever or tachycardia. Secondary closure of an open wound is acceptable in the absence of infection once the wound bed has entirely granulated. VAC is a reasonable alternative. Selection of a surgical dressing is dependent upon wound characteristics, with a goal of maintaining a moist environment. september 2012 magenta yellow cyan black contemporary ob/gyn 45 ES119853_obgyn0912_045.pgs 08.28.2012 13:22 ADV SURGICAL WOUNDS Syst. Rev. 2009;3(3), CD003677. 10. Summitt RL,Jr, Stovall TG, Steege JF, Lipscomb GH. A multicenter randomized comparison of laparoscopically assisted vaginal hysterectomy and abdominal hysterectomy in abdominal hysterectomy candidates. Obstet Gynecol 1998;92(3):321-326. 11. Swank HA, Mulder IM, la Chapelle CF, Reitsma JB, Lange JF, Bemelman WA. Systematic review of trocar-site hernia. Br J Surg. 2012;99(3):315-323. 12. Nagachinta T, Stephens M, Reitz B, Polk BF. Risk factors for surgicalwound infection following cardiac surgery. J Infect Dis. 1987;156(6):967-973. 13. Alanis MC, Villers MS, Law TL, Steadman EM, Robinson CJ. Complications of cesarean delivery in the massively obese parturient. Am J Obstet Gynecol. 2010;203(3):271.e1-271.e7. 14. King JT,Jr, Goulet JL, Perkal MF, Rosenthal RA. Glycemic control and infections in patients with diabetes undergoing noncardiac surgery. Ann Surg 2011;253(1):158-165. 15. Velander P, Theopold C, Hirsch T, et al. Impaired wound healing in an acute diabetic pig model and the effects of local hyperglycemia. Wound Repair and Regeneration. 2008;16(2):288-293. 16.Vermillion ST, Lamoutte C, Soper DE, Verdeja A. Wound infection after cesarean: effect of subcutaneous tissue thickness. Obstet Gynecol. 2000;95(6 Pt 1):923-926. 17. Neumayer L, Hosokawa P, Itani K, El-Tamer M, Henderson WG, Khuri SF. Multivariable predictors of postoperative surgical site infection after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg. 2007;204(6):1178-1187. 18. Jensen JA, Goodson WH, Hopf HW, Hunt TK. Cigarette smoking decreases tissue oxygen. Arch Surg. 1991;126(9):1131-1134. 19. Kathiresan AS, Brookfield KF, Schuman SI, Lucci JA,3rd. Malnutrition as a predictor of poor postoperative outcomes in gynecologic cancer patients. Arch Gynecol Obstet. 2011;284(2):445-451. 20. Martindale RG, McClave SA, Vanek VW, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition: Executive Summary. Crit Care Med. 2009;37(5):1757-1761. 21. Ashcroft GS, Mills SJ, Lei K, et al. Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor. J Clin Invest. 2003;111(9):1309-1318. 22. Routley CE, Ashcroft GS. Effect of estrogen and progesterone on macrophage activation during wound healing. Wound Repair Regen. 2009;17(1):42-50. 23. Carr BR, Parker CR,Jr, Madden JD, MacDonald PC, Porter JC. Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. Am J Obstet Gynecol. 1981;139(4):416-422. 24. Oxlund H, Fogdestam I, Viidik A. The influence of cortisol on wound healing of the skin and distant connective tissue response. Surg Gynecol Obstet. 1979;148(6):876-880. 25. Riou JP, Cohen JR, Johnson H, Jr. Factors influencing wound dehiscence. Am J Surg. 1992;163(3):324-330. 26. Andreassen TT, Fogdestam I, Rundgren A. A biomechanical study of healing of skin incisions in rats during pregnancy. Surg Gynecol Obstet. 1977;145(2):175-178. 27. Walsh CA, Tang T, Walsh SR. Laparoscopic versus open appendicectomy in pregnancy: a systematic review. Int J Surg. 2008;6(4):339-344. 28. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol. 1999;20(4):250-278; quiz 279-280. 29. Webster J, Osborne S. Preoperative bathing or showering with skin antiseptics to prevent surgical site infection. Cochrane Database Syst. Rev. 2007;(2)(2), CD004985. 30. Johnson AJ, Daley JA, Zywiel MG, Delanois RE, Mont MA. Preoperative chlorhexidine preparation and the incidence of surgical site infections after hip arthroplasty. J Arthroplasty. 2010;25(6 Suppl):98-102. 31. Darouiche RO, Wall MJ,Jr, Itani KM et al. Chlorhexidine-Alcohol versus Povidone-Iodine for Surgical-Site Antisepsis. N Engl J Med. 2010;362(1):18-26. 32. Stulberg JJ, Delaney CP, Neuhauser DV, Aron DC, Fu P, Koroukian SM. Adherence to surgical care improvement project measures and the association with postoperative infections. JAMA. 2010;303(24):2479-2485. 46 black contemporaryobgyn.net 33. O’Grady H, Baker E. Prevention of surgical site infections. Surgery (Oxford). 2011;29(10):513-517. 34. Owens CD, Stoessel K. Surgical site infections: epidemiology, microbiology and prevention. J Hosp Infect. 2008;70 Suppl 2:3-10. 35. ACOG Committee on Practice Bulletins--Gynecology. ACOG practice bulletin No. 104: antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol. 2009;113(5):1180-1189. 36. Smaill FM, Gyte GM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database Syst. Rev. 2010;(1)(1), CD007482. 37. Costantine MM, Rahman M, Ghulmiyah L et al. Timing of perioperative antibiotics for cesarean delivery: a metaanalysis. Am J Obstet Gynecol. 2008;199(3):301.e1-301.e6. 38. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 120: Use of prophylactic antibiotics in labor and delivery. Obstet Gynecol. 2011;117(6):1472-1483. 39. Webster J, Alghamdi AA. Use of plastic adhesive drapes during surgery for preventing surgical site infection. Cochrane Database Syst. Rev. 2007;(4)(4), CD006353. 40. Misteli H, Weber WP, Reck S et al. Surgical glove perforation and the risk of surgical site infection. Arch Surg. 2009;144(6):553-8; discussion 558. 41. Leong G, Wilson J, Charlett A. Duration of operation as a risk factor for surgical site infection: comparison of English and US data. J Hosp Infect. 2006;63(3):255-262. 42. Moslemi-Kebria M, El-Nashar SA, Aletti GD, Cliby WA. Intraoperative hypothermia during cytoreductive surgery for ovarian cancer and perioperative morbidity. Obstet Gynecol. 2012;119(3):590-596. 43. Hellums EK, Lin MG, Ramsey PS. Prophylactic subcutaneous drainage for prevention of wound complications after cesarean delivery--a metaanalysis. Am J Obstet Gynecol. 2007;197(3):229-235. 44. Clay FS, Walsh CA, Walsh SR. Staples vs subcuticular sutures for skin closure at cesarean delivery: a metaanalysis of randomized controlled trials. Am J Obstet Gynecol. 2011;204(5):378-383. 45. Ong J, Ho KS, Chew MH, Eu KW. Prospective randomised study to evaluate the use of DERMABOND ProPen (2-octylcyanoacrylate) in the closure of abdominal wounds versus closure with skin staples in patients undergoing elective colectomy. Int J Colorectal Dis. 2010;25(7):899-905. 46. Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG. CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections. Am J Infect Control. 1992;20(5):271-274. 47. Cutting KF, White RJ. Criteria for identifying wound infection-revisited. Ostomy Wound. Manage. 2005;51(1):28-34. 48. Kulaylat MN, Dayton MT. Surgical Complications. In: Sabiston Textbook of Surgery. Townsend CM, Beauchamp RD, Evers BM and Mattox KL(Eds.), Saunders, Philadelphia, 328 (2008). 49. Stevens DL, Bisno AL, Chambers HF et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. 2005;41(10):1373-1406. 50. Okan D, Woo K, Ayello EA, Sibbald G. The role of moisture balance in wound healing. Adv Skin Wound Care. 2007;20(1):39-53; quiz 53-5. 51. Bolton LL, Monte K, Pirone LA. Moisture and healing: beyond the jargon. Ostomy Wound Manage. 2000;46(1A Suppl):51S-62S; quiz 63S-64S. 52. Narducci F, Samouelian V, Marchaudon V et al. Vacuum-assisted closure therapy in the management of patients undergoing vulvectomy. Eur J Obstet Gynecol Reprod Biol. 2012;161(2):199-201. 53. Gregor S, Maegele M, Sauerland S, Krahn JF, Peinemann F, Lange S. Negative pressure wound therapy: a vacuum of evidence? Arch Surg. 2008;143(2):189-196. 54. Walsh C, Scaife C, Hopf H. Prevention and management of surgical site infections in morbidly obese women. Obstet Gynecol. 2009;113(2 Pt 1):411-415. 55. Morykwas MJ, Simpson J, Punger K, Argenta A, Kremers L, Argenta J. Vacuum-assisted closure: state of basic research and physiologic foundation. Plast Reconstr Surg. 2006;117(7 Suppl):121S-126S. 56. Scherer SS, Pietramaggiori G, Mathews JC, Prsa MJ, Huang S, Orgill DP. The mechanism of action of the vacuum-assisted closure device. Plast Reconstr Surg. 2008;122(3):786-797. 57. Dodson MK, Magann EF, Meeks GR. A randomized comparison of secondary closure and secondary intention in patients with superficial wound dehiscence. Obstet Gynecol.1992;80(3 Pt 1);321-324. 58. Schimp VL, Worley C, Brunello S et al. Vacuum-assisted closure in the treatment of gynecologic oncology wound failures. Gynecol Oncol. 2004;92(2):586-591. september 2012 ES119852_obgyn0912_046.pgs 08.28.2012 13:22 ADV Discover Where Innovation Can Take You With World’s-Only Technologies Autoclavable 5 mm HD Deflectable-Tip Video Laparoscope Fully-Integrated Ultrasonic and Advanced Bipolar Technology Only Olympus has the comprehensive platform of products that you need to perform every step of Laparo-Endoscopic Single-Site (LESS) Surgery Access Ports Visualization Platform Advanced Energy Devices For more information, call 888-524-7266 to speak to a sales representative © 2012 Olympus America Inc. Trademark or Registered Trademark of Olympus or its affiliate entities in the U.S. and/or other countries of the world. All patents apply. AD805-0812 magenta yellow cyan black ES110991_OBGYN0912_047_FP.pgs 08.20.2012 23:33 ADV BY DAVID A. MILLER, MD Fetal heart rate monitoring and the cesarean delivery rate The sixth article in the Electronic Fetal Monitoring Mythbusters series examines the scientific evidence behind the familiar claim that electronic fetal heart rate monitoring increases the cesarean delivery rate. I n this series, we have reviewed standard electronic fetal monitoring (EFM) nomenclature, challenged common notions about fetal heart rate (FHR) decelerations, and exposed a specious theory concerning intrapartum fetal head compression. This month’s article will examine the evidence underlying the common perception that EFM increases the cesarean delivery rate. History When EFM replaced the traditional practice of intermittent auscultation in the 1970s, a series of studies reported significantly lower perinatal mortality rates in electronically monitored patients.1-11 These studies were nonrandomized, and employed nonconcurrent controls, leading some to cite unrelated and simultaneous improvements in neonatal care and falling perinatal mortality rates as possible sources of bias. MacDonald and Grant pointed out that, over the time period of these studies, hospitals not using EFM also experienced rates of improvement in perinatal outcome similar to those seen in hospitals using EFM.12 Despite the well-known shortcomings of nonrandomized trials, these studies had the effect of validating use of EFM. In 1976, the first of a series of randomized, controlled trials was published, comparing EFM to intermittent auscultation of the FHR during labor.13 To date, 12 such studies have been published, 10 of which included data on overall cesarean delivery rates.13-23 These trials are summarized in the Table (see page 50). Randomized controlled trials of EFM versus auscultation In 1976, Haverkamp and colleagues reported the first prospective randomized study of 483 high-risk 48 magenta yellow cyan black CONTEMPORARYOBGYN.NET obstetric patients, comparing EFM with intermittent FHR auscultation in labor.13 There were no significant differences in perinatal mortality, Apgar scores, cord blood pH values, or neonatal morbidity between the EFM and control groups. The monitored group, however, had a significantly higher rate of cesarean delivery compared with the auscultated group (16.5% vs 6.6%, respectively). A second study by Renou and colleagues in 1976 randomized 350 high-risk patients to EFM or intermittent auscultation during labor.14 There were no significant differences between the groups with respect to perinatal mortality, Apgar scores, or maternal or neonatal infection. Patients in the monitored group, however, had significantly higher umbilical cord blood pH values, significantly lower rates of admission to the neonatal intensive care unit (NICU), fewer neonatal neurologic signs or symptoms, and fewer cases of neonatal brain damage (not further defined). The cesarean delivery rate was again significantly higher in the monitored group than in the control group (22.3% vs 13.7%, respectively). In 1978, Kelso and associates published a randomized controlled trial comparing EFM with intermittent auscultation in 504 low-risk patients.15 There were no significant differences between the groups with respect to perinatal mortality, low Apgar scores, cord blood pH values, NICU admissions or lengths of stay, neonatal or maternal infections, or abnormal neonatal neurologic findings. The only significant difference between the If you have a question on EFM, we’d like to hear from you. Those of interest to a wide audience will be answered in future installments of EFM Mythbusters. Send your question to [email protected]. SUBMIT YOUR CLINICAL QUESTION SEPTEMBER 2012 ES119664_obgyn0912_048.pgs 08.28.2012 11:41 ADV groups was an increase in incidence of cesarean birth in monitored patients compared with auscultated patients (9.5% vs 4.4%, respectively). In 1979, Haverkamp and colleagues published another randomized controlled trial in high-risk patients. The design was similar to their first study, but additional measures of infant status were included as well as the option to perform fetal scalp pH determination during labor.16 A total of 690 high-risk patients were randomized into 3 groups. In the first group, fetal assessment during labor was accomplished by intermittent auscultation. The second group had continuous EFM alone, and the third group had continuous EFM with the option to measure scalp blood pH as needed. Among the 3 groups, no significant differences were seen in perinatal mortality, Apgar scores, cord blood pH values, maternal or neonatal infectious morbidity, NICU admissions, or neonatal neurologic abnormalities. A significantly increased incidence of cesarean birth was demonstrated in the group with EFM alone (18%) compared with auscultation alone (6%). The option to perform scalp blood sampling resulted in an intermediate cesarean delivery rate (11%) that was not significantly different from either of the other groups. In 1981, a fifth trial was published by Wood and colleagues.17 A total of 989 low-risk patients were randomized to EFM or intermittent auscultation. No significant differences between the groups were seen in perinatal mortality, Apgar scores, cord blood pH values, NICU admissions, or neonatal neurologic abnormalities. In this study, the cesarean delivery rates were not significantly different between the groups (4% in the monitored group vs 2% in the auscultated group). In 1985, MacDonald and colleagues published a randomized controlled trial comparing EFM with intermittent auscultation in 12,964 pregnancies.18 It was the first study in which the sample size needed to demonstrate statistically significant differences between the groups was prospectively calculated. The authors calculated that 13,000 patients would be needed to demonstrate a 50% reduction in combined incidence of intrapartum stillbirths, neonatal deaths, and neonatal seizures in survivors (power 75%, P<.05). Again there were no significant differences between the groups in Meet our Deputy Editor JON I. EINARSSON, MD, MPH at AAGL Visit Contemporary OB/GYN in Publisher’s Row at the AAGL’s 41st Global Congress in Las Vegas where you can meet Dr. Einarsson and share your comments and ideas for Contemporary OB/GYN. Dr. Einarsson is Associate Professor of Obstetrics and Gynecology at Harvard Medical School and Director, Division of Minimally Invasive Gynecologic Surgery, Brigham and Women’s Hospital. Join him on Wednesday, November 7 from noon to 1.30 p.m. No appointment is necessary. magenta yellow cyan black ES119661_obgyn0912_049.pgs 08.28.2012 11:41 ADV TABLE Randomized trials comparing EFM with intermittent auscultation Publication Date No. Patients EFM Impact on Cesarean Rate Haverkamp, et al13 1976 483 Increase Renou, et al14 1976 350 Increase Kelso, et al15 1978 504 Increase Author Haverkamp, et al16 1979 690 Increase Wood, et al17 1981 989 No increase MacDonald, et al18 1985 12,964 No increase 19 Neldam, et al 1986 969 No increase Luthy, et al21 1987 246 No increase Vintzileos, et al22 1993 1,428 No increase 1994 4,044 No increase 23 Herbst, et al Abbreviation: EFM, electronic fetal monitoring. perinatal mortality, low Apgar scores, neonatal trauma, resuscitation requirement, NICU admissions, or infectious morbidity. Significantly more cases of neonatal seizures and persistent neurologic abnormalities (>1 week) were seen in the control group, but at 1-year and 4-year follow-ups, no differences remained in rates of children with neurologic abnormalities (3 cases in each group).24 The cesarean delivery rate in the EFM group (2.4%) was not significantly different from that in the auscultated group (2.2%). In 1986, Neldam and associates reported a randomized controlled trial of EFM versus intermittent auscultation in 969 combined low- and high-risk patients.19 There were no significant differences between the groups with respect to perinatal mortality, low Apgar scores, seizures, NICU admissions, length of NICU stay, or cesarean delivery. Also in 1986, Leveno and colleagues published a randomized trial comparing universal monitoring with “selective” monitoring in 34,995 pregnancies.20 Of these pregnancies, 14,618 were considered “low risk” and were managed during labor with either selective (n=7,330) or universal (n=7,228) electronic monitoring. Perinatal mortality, 5-minute Apgar scores, NICU admissions, ventilator requirement, and neonatal seizures were similar in the 2 groups. More cases of “abnormal FHR” were observed in the monitored group, leading to significantly more cesarean deliveries for “fetal distress” (9% vs 4%). However, overall cesarean rates were not reported. In 1987, Luthy and colleagues compared EFM and intermittent auscultation in 246 high-risk patients with preterm labor. 21 There were no significant differences between the groups with respect to perinatal mortality, 50 magenta yellow cyan black CONTEMPORARYOBGYN.NET low Apgar scores, cord pH values, neonatal seizures, respiratory distress syndrome (RDS), intracranial hemorrhage, or cesarean delivery rates (EFM, 15.6%; controls, 15.2%). In 1993, Vintzileos and colleagues compared EFM and intermittent auscultation in 1,428 patients in a population with high baseline perinatal mortality rates of 20.4 to 22.6 per 1,000.22 Significantly fewer perinatal deaths occurred in the EFM group (2.6/1,000 vs 13/1,000). Furthermore, no “hypoxia-related” perinatal deaths were reported in the EFM group, whereas 6 such deaths occurred in the auscultation group (0.9%), a difference that was statistically significant (P=.03). The groups did not differ significantly with respect to low Apgar scores, NICU admissions or lengths of stay, ventilator requirements, neonatal hypoxicischemic encephalopathy, intraventricular hemorrhage, seizures, hypotonia, necrotizing enterocolitis, RDS, or cesarean delivery rate (9.5% in electronically-monitored patients vs 8.6% in controls). The final study by Herbst and Ingemarrson in 1994 compared outcomes in 2,029 labors managed with continuous EFM and 2,015 labors managed with intermittent auscultation alternating with intermittent EFM.23 There were no differences between the groups with respect to Apgar scores, umbilical artery pH values, NICU admissions, or cesarean delivery rates. Meta-analyses In 2006, a Cochrane review that included the above studies concluded that EFM was associated with an increased rate of cesarean delivery compared with intermittent FHR auscultation during labor.25 Over the years, this familiar contention has assumed the mantle of conventional wisdom.26 However, a slightly different analysis of the exact same data can lead to a very different conclusion. In the 1970s, the first years after the introduction of EFM, 4 randomized trials compared the new technology to the previous standard of intermittent FHR auscultation during labor. Together, these 4 trials included 2,027 patients, and each of the 4 trials demonstrated a significantly higher rate of cesarean birth in electronically monitored patients. In the ensuing 3 decades, 7 randomized trials were published on the same topic, 6 of which included data regarding overall cesarean rates. These 6 trials included a total of 20,640 patients, more than 10 times the number of patients included in the studies published before 1980. Interestingly, none of the trials published after 1980 demonstrated a higher rate of cesarean delivery in women managed with EFM compared with those managed with intermittent auscultation (Table). SEPTEMBER 2012 ES119888_obgyn0912_050.pgs 08.28.2012 13:55 ADV WE’RE CHANGING THE WAY OVARIAN CANCER PATIENTS FEEL ABOUT THE FUTURE Intraperitoneal (IP) chemotherapy was introduced as a way to treat ovarian cancer by administering chemotherapy directly to the abdomen rather than through a vein. While this treatment extended median survival for women, the side effects were harsh and many women were unable to complete treatment. Our faculty at Magee-Womens Hospital of UPMC and UPMC CancerCenter played a major role in the adaptation of IP to a modern outpatient regimen, reducing side effects and improving outcomes by adjusting dosing and anticipating and controlling symptoms. Oncologists at Magee and throughout UPMC were also among the first to use hyperthermic IP chemotherapy for the treatment of ovarian cancer. Learn more at UPMCPhysicianResources.com/OvarianCancer. UPMC is affiliated with the University of Pittsburgh School of Medicine. magenta yellow cyan black ES110993_OBGYN0912_051_FP.pgs 08.20.2012 23:33 ADV A realistic appraisal of the relationship between EFM and cesarean delivery rates must take into account the steep learning curve that defined the early years of the new technology. By the early 1980s, it appeared that the learning curve had reached a plateau. What might have seemed true in the 1970s was not confirmed by subsequent studies. Contemporary data published since 1980 simply do not support the prevailing sentiment that EFM increases the rate of cesarean delivery compared with intermittent auscultation conducted as prescribed in research protocols. This recognition may not have a significant impact on the day-to-day practice of obstetrics. However, it highlights the axiom “You can’t believe everything you hear.” It also raises the question that has been the focus of this series: How many popular EFM beliefs are not supported by contemporary evidence? Continued forward progress in the area of fetal monitoring will require heightened awareness by all stakeholders of the difference between conclusions drawn from contemporary scientific evidence and those derived from outdated or insufficient evidence fortified by mere repetition. This series will continue in 2 months with an analysis of the value of EFM as a screening test. DR MILLER is professor of clinical obstetrics, gynecology, and pediatrics in the Division of Maternal-Fetal Medicine, Keck School of Medicine, University of Southern California, Los Angeles, and in the Department of Pediatrics, Children’s Hospital Los Angeles. He is a consultant for Clinical Computer Systems and is in partnership with GE Healthcare to promote multidisciplinary fetal monitoring education. REFERENCES 1. Chan WH, Paul RH, Toews J. Intrapartum fetal monitoring. Maternal and fetal morbidity and perinatal mortality. Obstet Gynecol. 1973;41(1):7-13. 2. Kelly VC, Kulkarni D. Experiences with fetal monitoring in a community hospital. Obstet Gynecol. 1973;41(6):818-824. 3. Tutera G, Newman RL. Fetal monitoring: its effect on the perinatal mortality and caesarean section rates and its complications. Am J Obstet Gynecol. 1975;122(6):750-754. 4. Sibanda J, Beard RW. Influence on clinical practice of routine intra-partum fetal monitoring. Br Med J. 1975;3(5979):341-343. 5. Shenker L, Post RC, Seiler JS. Routine electronic monitoring of fetal heart rate and uterine activity during labor. Obstet Gynecol. 1975;46(2):185-189. 6. Koh KS, Greves D, Yung S, Peddle LJ. Experience with fetal monitoring in a university teaching hospital. Can Med Assoc J. 1975;112(4):455-456, 459-460. 7. Lee WK, Baggish MS. The effect of unselected intrapartum fetal monitoring. Obstet Gynecol. 1976;47(5):516-520. 52 magenta yellow cyan black CONTEMPORARYOBGYN.NET 8. Paul RH, Huey JR Jr, Yaeger CF. Clinical fetal monitoring: its effect on cesarean section rate and perinatal mortality: five-year trends. Postgrad Med. 1977;61(4):160-166. 9. Amato JC. Fetal monitoring in a community hospital. A statistical analysis. Obstet Gynecol. 1977;50(3):269-274. 10. Johnstone FD, Campbell DM, Hughes GJ. Has continuous intrapartum monitoring made any impact on fetal outcome? Lancet. 1978;1(8077):1298-1300. 11. Hamilton LA Jr, Gottschalk W, Vidyasagar D, Horn C, Wynn RM. Effects of monitoring high-risk pregnancies and intrapartum FHR monitoring on perinates. Int J Gynaecol Obstet. 1978;15(6):483-490. 12. MacDonald D, Grant A. Fetal surveillance in labour—the present position. In: Bonnar J, ed. Recent Advances in Obstetrics and Gynaecology, No. 15. London: Churchill Livingstone; 1987:83-100. 13. Haverkamp AD, Thompson HE, McFee JG, Cetrullo C. The evaluation of continuous fetal heart rate monitoring in high-risk pregnancy. Am J Obstet Gynecol. 1976;125(3):310-320. 14. Renou P, Chang A, Anderson I, Wood C. Controlled trial of fetal intensive care. Am J Obstet Gynecol. 1976;126(4):470-476. 15. Kelso IM, Parsons RJ, Lawrence GF, Arora SS, Edmonds DK, Cooke ID. An assessment of continuous fetal heart rate monitoring in labor. A randomized trial. Am J Obstet Gynecol. 1978;131(5):526-532. 16. Haverkamp AD, Orleans M, Langendoerfer S, McFee J, Murphy J, Thompson HE. A controlled trial of the differential effects of intrapartum fetal monitoring. Am J Obstet Gynecol. 1979;134(4):399-412. 17. Wood C, Renou P, Oats J, Farrell E, Beischer N, Anderson I. A controlled trial of fetal heart rate monitoring in a low-risk obstetric population. Am J Obstet Gynecol. 1981;141(5):527-534. 18. MacDonald D, Grant A, Sheridan-Pereira M, Boylan P, Chalmers I. The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring. Am J Obstet Gynecol. 1985;152(5):524-539. 19. Neldam S, Osler M, Hansen PK, Nim J, Smith SF, Hertel J. Intrapartum fetal heart rate monitoring in a combined low- and high-risk population: a controlled clinical trial. Eur J Obstet Gynecol Reprod Biol. 1986;23(1-2):1-11. 20. Leveno KJ, Cunningham FG, Nelson S, et al. A prospective comparison of selective and universal electronic fetal monitoring in 34,995 pregnancies. N Engl J Med. 1986;315(10):615-619. 21. Luthy DA, Shy KK, van Belle G, et al. A randomized trial of electronic fetal monitoring in preterm labor. Obstet Gynecol. 1987;69(5):687-695. 22. Vintzileos AM, Antsaklis A, Varvarigos I, Papas C, Sofatzis I, Montgomery JT. A randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent auscultation. Obstet Gynecol. 1993;81(6):899-907. 23. Herbst A, Ingemarsson I. Intermittent versus continuous electronic fetal monitoring in labour: a randomised study. Br J Obstet Gynaecol. 1994;101(8):663–668. 24. Grant A, O’Brien N, Joy MT, Hennessy E, MacDonald D. Cerebral palsy among children born during the Dublin randomised trial of intrapartum monitoring. Lancet. 1989;2(8674):1233-1236. 25. Alfirevic Z, Devane D, Gyte GM. Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour. Cochrane Database Syst Rev. 2006;(3):CD006066. 26. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 106: Intrapartum fetal heart monitoring: nomenclature, interpretation, and general management principles. Obstet Gynecol. 2009;114(1):192-202. SEPTEMBER 2012 ES119662_obgyn0912_052.pgs 08.28.2012 11:41 ADV magenta yellow cyan black ES110959_OBGYN0912_053_FP.pgs 08.20.2012 23:32 ADV ACOG GUIDELINES AT A GLANCE EXPERT PERSPECTIVES ON PRACTICE BULLETINS Committee on Practice Bulletins—Obstetrics ACOG Practice Bulletin No 127: Management of Preterm Labor, June 2012 Obstet Gynecol 2012;119:1308-17. Full text of ACOG Practice Bulletin available to ACOG members at http://www.acog.org/ Resources_And_Publications/Practice_Bulletins/Committee_on_Practice_Bulletins_--_Obstetrics/Management_of_Preterm_Labor Management of Preterm Labor Preterm birth is the leading cause of neonatal mortality and the most common reason for antenatal hospitalization (1–4). In the United States, approximately 12% of all live births occur before term, and preterm labor preceded approximately 50% of these preterm births (5, 6). Although the causes of preterm labor are not well understood, the burden of preterm births is clear—preterm births account for approximately 70% of neonatal deaths and 36% of infant deaths as well as 25–50% of cases of long-term neurologic impairment in children (7–9). A 2006 report from the Institute of Medicine estimated the annual cost of preterm birth in the United States to be $26.2 billion or more than $51,000 per premature infant (10). However, identifying women who will give birth preterm is an inexact process. The purpose of this document is to present the various methods proposed to manage preterm labor and to review the evidence for the roles of these methods in clinical practice. Identification and management of risk factors for preterm labor are not addressed in this document. Used with permission. Copyright the American College of Obstetricians and Gynecologists. C O M M E N TA RY Management of preterm labor: Have we learned anything since 2003? By Sarah J. Kilpatrick, MD, PhD Dr. Kilpatrick is Chair, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, and a member of the Contemporary OB/GYN Editorial Board. The answer is yes, with a few caveats. In the last 9 years, we have learned at least 2 new things about the management of preterm labor or, really, about interventions for women likely to deliver early that reduce morbidity for their newborns. Sad but true, however, is that we really have not learned anything new that helps us prevent or delay preterm delivery. The other sad truth is that we are still employing useless interventions to attempt to delay preterm delivery and the American College of Obstetricians and Gynecologists (ACOG) continues to try to help us just stop, first with the recommendations in its 2003 practice bulletin and now by reaffirming that same information in the 2012 practice bulletin on the same subject.1 First, the new things: Antenatal corticosteroids. This is listed as a Level A recommendation in the 2012 bulletin.1 A single course of corticosteroids is recommended for 54 magenta yellow cyan black CONTEMPORARYOBGYN.NET pregnant women between 24 and 34 weeks who are at risk of preterm delivery within 7 days. The reason for this recommendation, of course, is that numerous randomized trials and a Cochrane meta-analysis show a significant reduction in neonatal morbidity and mortality—including respiratory distress syndrome, necrotizing enterocolitis, and intraventricular hemorrhage—with corticosteroids.2-4 New data from randomized trials also show that a single repeat course (2 doses) in women whose prior course was at least 7 days previously and who remain at risk of preterm delivery before 34 weeks significantly reduces neonatal morbidity.5,6 This latter recommendation is listed as Level B in the 2012 bulletin.1 Antenatal magnesium sulfate for fetal neuroprotection. This intervention for fetal neuroprotection is new and listed as Level A1: Magnesium sulfate reduces the severity and risk of cerebral palsy in surviving infants if administered when birth is anticipated before 32 weeks.7-11 It is also recommended that if a hospital elects to use magnesium sulfate for neuroprotection, guidelines be developed for inclusion criteria, treatment regimens, concurrent tocolysis, and monitoring in accordance with one of the larger trials. An excellent trial to use for possible guideline development is the Rouse trial.9 The other key Level A recommendation, which is similar between the 2 bulletins, is that any tocolysis is effective only for a short time (2 days), which reinforces that all we can really do is stop labor long enough to gain the neonatal benefit of antenatal corticosteroids and magnesium sulfate.1 SEPTEMBER 2012 ES120264_obgyn0912_054.pgs 08.29.2012 11:38 ADV ACOG GUIDELINES AT A GLANCE Second, the things we need to stop doing: Maintenance tocolysis. Tocolysis with any drug used outside the 2-day window to allow antenatal steroids does not work.1,12-14 It did not work in 2003 and it still does not work in 2012.1 There are numerous randomized trials to this effect, so stop using it (Level A evidence in 2003 and 2012). The labeling for terbutaline even includes a black box warning, which was added by the US Food and Drug Administration in 2011 because of deleterious maternal side effects.14 Antibiotics for prolongation of pregnancy. They still do not work (Level A evidence in 2003 and 2012).1,15 Bed rest and hydration. They still have not been shown to have any impact on prolonging pregnancy and may be harmful. Bed rest and hydration should not be routinely recommended to women with preterm labor (listed as Level B evidence in 2003 and 2012).1 The other new addition to the 2012 bulletin is the proposed performance measure, which is ACOG’s suggestion for what might be used for recertification by the American Board of Medical Specialties as part of maintenance of certification sometime in the future.1 The proposed performance measure is “the proportion of women with preterm labor at less than 34 weeks of gestation who receive corticosteroid therapy.” Finally, predictors of preterm delivery (fetal fibronectin and ultrasound cervical length) remain useful only for their negative predictive value and “should not be used exclusively to direct management in the setting of acute symptoms” (Level B evidence in the 2012 bulletin).1,16 The bottom line So what can we do for our patients with preterm labor and intact membranes between 24 and 34 weeks’ gestation? In this case, less is more. Treat with tocolytics acutely only to gain time for the benefit of corticosteroids and magnesium sulfate for neuroprotection (follow your protocol for magnesium sulfate for neuroprotection). Stop maintenance tocolysis, use of antibiotics (except to prolong latency following preterm membrane rupture between 24 and 35 weeks), and routine use of hydration and bed rest. C O M M E N TA RY R E F E R E N C E S 1. ACOG practice bulletin no. 127: management of preterm labor. Obstet Gynecol. 2012;119(6):1308-1317. 2. Antenatal corticosteroids revisited: repeat courses. NIH Consens Statement. 2000;17(2):1-18. 3. Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;(3):CD004454. 4. Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994;12(2):1-24. 5. Garite TJ, Kurtzman J, Maurel K, Clark R; Obstetrix Collaborative Research Network. Impact of a ‘rescue course’ of antenatal corticosteroids: a multicenter randomized placebo-controlled trial. Am J Obstet Gynecol. 2009;200(3):248. e1-248.e9. Erratum in: Am J Obstet Gynecol. 2009;201(4):428]. 6. Crowther CA, McKinlay CJ, Middleton P, Harding JE. Repeat doses of prenatal corticosteroids for women at risk of preterm birth for improving neonatal health outcomes. Cochrane Database Syst Rev. 2011;(6):CD003935. 7. Crowther CA, Hiller JE, Doyle LW, Haslam RR; Australasian Collaborative Trial of Magnesium Sulphate (ACTOMg SO4) Collaborative Group. Effect of magnesium sulfate given for neuroprotection before preterm birth: a randomized controlled trial. JAMA. 2003;290(20):2669-2676. 8. Marret S, Marpeau L, Zupan-Simunek V, et al; PREMAG trial group. Magnesium sulphate given before very-preterm birth to protect infant brain: the randomised controlled PREMAG trial. BJOG. 2007;114(3):310-318. 9. Rouse DJ, Hirtz DG, Thom E, et al; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med. 2008;359(9):895-905. 10. Conde-Agudelo A, Romero R. Antenatal magnesium sulfate for the prevention of cerebral palsy in preterm infants less than 34 weeks’ gestation: a systematic review and metaanalysis. Am J Obstet Gynecol. 2009;200(6):595-609. 11. Han S, Crowther CA, Moore V. Magnesium maintenance therapy for preventing preterm birth after threatened preterm labour. Cochrane Database Syst Rev. 2010;(7):CD000940. 12. Dodd JM, Crowther CA, Dare MR, Middleton P. Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane Database Syst Rev. 2006;(1):CD003927. 13. Lyell DJ, Pullen KM, Mannan J, et al. Maintenance nifedipine tocolysis compared with placebo: a randomized controlled trial. Obstet Gynecol. 2008;112(6):1221-1226. 14. US Food and Drug Administration (FDA). FDA drug safety communication: new warnings against use of terbutaline to treat preterm labor. http://www. fda.gov/drugs/drugsafety/ucm243539.htm. Published February 17, 2011. Updated February 24, 2011. Accessed March 20, 2012. 15. King J, Flenady V. Prophylactic antibiotics for inhibiting preterm labour with intact membranes. Cochrane Database Syst Rev. 2002;(4):CD000246. 16. Berghella V, Hayes E, Visintine J, Baxter JK. Fetal fibronectin testing for reducing the risk of preterm birth. Cochrane Database Syst Rev. 2008(4):CD006843. ACOG ABSTRACT REFERENCES 1. Tucker JM, Goldenberg RL, Davis RO, Copper RL, Winkler CL, Hauth JC. Etiologies of preterm birth in an indigent population: is prevention a logical expectation? Obstet Gynecol 1991;77:343–7. (Level II-3) 2. Savitz DA, Blackmore CA, Thorp JM. Epidemiologic characteristics of preterm delivery: etiologic heterogeneity. Am J Obstet Gynecol 1991;164:467–71. (Level III) 3. Kramer MS. Preventing preterm birth: are we making any progress? Yale J Biol Med 1997;70:227–32. (Level III) 4. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Mathews TJ, Osterman MJ. Births: final data for 2008. Natl Vital Stat Rep 2010;59(1):1–72. Available at http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_01.pdf. Retrieved June 28, 2011. (Level II-3) 5. Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2009. Natl Vital Stat Rep 2010;59(3):1–19. Available at http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_03.pdf. Retrieved June 28, 2011. (Level II-3) 6. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet 2008;371:75–84. (Level III) 7. Volpe JJ. Overview: perinatal and neonatal brain injury. Ment Retard Dev Disabil Res Rev 1997;3:1–2. (Level III) 8. Mathews TJ, MacDorman MF. Infant mortality statistics from the 2006 period linked birth/infant death data set. Natl Vital Stat Rep 2010;58(17):1– 31. (Level II-3) 9. MacDorman MF, Callaghan WM, Mathews TJ, Hoyert DL, Kochanek KD. Trends in preterm-related infant mortality by race and ethnicity: United States, 1999-2004. NCHS Health E-Stat. Hyattsville (MD): National Center for Health Statistics; 2007. Available at: http://www.cdc.gov/nchs/ data/hestat/infantmort99-04/infantmort99-04.htm. Retrieved July 25, 2011. (Level II-3) 10. Institute of Medicine. Preterm birth: causes, consequences, and prevention. Washington, DC: National Academies Press; 2007. (Level III) SEPTEMBER 2012 magenta yellow cyan black CONTEMPORARY OB/GYN 55 ES119773_obgyn0912_055.pgs 08.28.2012 12:11 ADV Products & Services SHOWCASE Go to: products.modernmedicine.com Business Opportunities INVEST IN YOUR FUTURE MEDI-WEIGHTLOSS Search INCREASE REVENUE $ 60,444 PER MONTH† With our proven system and NO insurance claims to file! Wonder what these are? 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Search for the company name you see in each of the ads in this section for FREE INFORMATION! 56 magenta yellow cyan black ContemporaryObgyn.net SEPTEMBER 2012 ES120462_obgyn0912_056_CL.pgs 08.29.2012 15:42 ADV Go to: Products & Services SHOWCASE products.modernmedicine.com CME Workshop AMERICAN_ACADEMY_OF ANTI-AGING_MEDICINE Search NOw iNTRODuciNg ThE SExuAL hEALTh cERTificATiON MODuLE A: fEMALE SExuAL DYSfuNcTiON NOV 2-3, 2012 ENROLL TODAY! 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SEPTEMBER 2012 magenta yellow cyan black CONTEMPORARY OB/GYN 57 ES120618_obgyn0912_057_CL.pgs 08.29.2012 16:30 ADV MARKETPLACE For Products & Services Advertising, contact: Joan Maley (800) 225-4569 ext. 2722, [email protected] CONTINUING MEDICAL EDUCATION Are your Patients Asking for... Botox®? Learn about... Plus, Learn to Treat: Botox®/Fillers l Lasers l Skin Rejuvenation l l UP TO Smart editorial. Smart marketing. 15 Melasma Leg Veins l Age Spots l Acne CME CAT 1 S CREDIT l September 22-23, December 8-9 hCG for Weight Loss? 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By DaviD OB/GYN ENDOSCOPE REPAIR E Also... se trends: Heart disea looking Women are more like men fetal heart monitoring with this customiza handout: ble www.contemporar yobgyn.ne tracings t/ uvers Proper mane cia cases dysto in shoulder Pre-Owned Rigid & Flexible Scopes Etty ImagES We repair all Makes & Models of both Rigid & Flexible Scopes. No models are Obsolete!Substantial Savings! Prepare your patient for what to expect during Sam EdwardS /OJO ImagES/g SAVE MONEY! lectron ic fetal heart rate was introdu (FHR) ced of preven ting intrap in the late 1960s monitoring cerebral from the with the palsy (CP).1 artum fetal Ameri brain injury hope Gynec this hope Howev ologists can College of (ACOG First, the was unrealistic er, it is now clear and Pediat Obstetricians ), the Ameri rics (AAP) for at least false-positive that monit oring can Acade and Health , 2 reason and Huma the National my of for predic rate of intrap s. the Except Institute artum Internationa n Develo ting in of Child FHR pment FHR monitothe most extrem CP exceed (NICHD), A growin l Cerebral Palsy s 2 and g body predicting ring has never e cases, intrap 99%. standa of eviden Taskforce. artum rdizat outsid e CP. Second, mostbeen capable of ce indica can reduce ion of intrap the intrap reliably tes that cases of artum advers e cannot liabili ty artum mana gemen be period CP originate claims . 4,5 outcom es and monitoring prevented by and standardizati profes sionalt Howe ver, theref any form or on of for of intrapa ore by lack It is time intervention. 3 rtum of consen FHR monitoring many years, to set aside and to standa was imped focus instea unrealistic rdizat ion, sus. Witho ut ed based eviden clear guidan clinici ans d on practi expectations metho ds were left ce-bas ed benefits cal, eviden to maxim unfounded ce and ofen of intrap ceize the accusations found themse withou t articl e artum In recent lves facing review of FHR monit poten tial misma s the intrapartum nagement. made toward years, signifi oring. This evolvi ng consensus cant progre ss interp retatio FHR monito conse result, the ring nomen nsus in has in n and appro ach a reality prospect of standaFHR monitoring. been presen clature As rdization The areas to intrap artumts a simple , practiand eviden . Standardizat has becom a cal additi ce-bas ed consen ion must peer-revieweof consen sus FHR mana e reflect gemen on, it are d literat must be sus in the literat current ure, includdrawn from t. teachable. simple A logica ing public the FHR , practi ure. In l first monit cal, ations definition, oring into step is to decons and interpretation its essent truct , and managial eleme nts: ement. Sales | Repair | Pre-Owned Video Camera Systems | Bovie Units | Light Sources Savings on German Instruments GE Ultrasound Systems | Probe Repair E.C. 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SEPTEMBER 2012 ES120481_obgyn0912_058_CL.pgs 08.29.2012 15:43 ADV MARKETPLACE SEMINARS MEDICAL EQUIPMENT FOR PRODUCTS & SERVICES ADVERTISING Contact: Joan Maley (800) 225-4569 ext. 2722 • [email protected] SEMINARS SEPTEMBER 2012 magenta yellow cyan black CONTEMPORARY OB/GYN 59 ES120471_obgyn0912_059_CL.pgs 08.29.2012 15:42 ADV RECRUITMENT For Recruitment Advertising, contact: Jacqueline Moran (800) 225-4569 ext. 2762, [email protected] NATIONAL FLORIDA ORLANDO AReA 45 Minute From Te Beach! Seeking BC/BE OB/GYN physician to join 5 physician group Level 3 hospital ~ No emergency room call Income potential unlimited Send CV to e-mail: [email protected] or fax: 407-209-3575 Check out our website @ www.wcorlando.com For more information, please call 407-418-9103 CALIFORNIA GEORGIA Santa Barbara Gyn Practice For Sale Well established 35 year old office gyn and gyn surgery (optional obstetrics) practice for sale in beautiful coastal Santa Barbara in newly renovated modern office next door to brand new state-of-the-art 500 bed hospital. Modern office equipment and furniture in turn key transition including dedicated office staff. Negotiable price. Excellent income potential. OBGYN Search, 800-831-5475, Fax:314-984-8246, [email protected], www.obgynpractices.com CONNECTICUT FLORIDA FLORIDA OB/GYN Family Health Centers of Southwest Florida, Inc. (FHC) is a private, not for profit, multi-specialty, Federally Qualified Healthcare Center and has been Joint Commission accredited for 15 years. Headquartered in beautiful Fort Myers, Florida, our community health center was established in the mid 1960’s and now employs about 300 with a $30 Million Budget, and still growing. Illinois Hospital employed obgyn position taking over for retiring physician with busy practice joining one employed obgyn in family oriented community with close proximity to Peoria and three hours to St. Louis/Chicago associated with a modern and financially stable 124 bed hospital doing 275 annual deliveries. Brand new state-of-the-art office. 4 day work week with 1-2 call. Excellent salary, bonus and benefits. OBGYN Search 800-831-5475, [email protected], www.obgynpractices.com Join well established three physician obgyn private practice in desirable affluent northern suburbs 45 minutes to downtown Chicago associated with a modern 156 bed hospital doing 2000 annual deliveries with daVinci Robotics. Modern office next door to hospital. 1-3 call. Excellent salary, bonus, benefits and future partnership. OBGYN Search, 800-831-5475 [email protected], www.obgynpractices.com FHC is offering a great opportunity for an experienced Board Certified OB/GYN; Bilingual English-Spanish preferred. Competitive Salary and Comprehensive Benefits Package including Malpractice Insurance and possible loan repayment. Respond to [email protected] or Fax (239) 278-3203. EOE/Drug Free Please visit our website at www.fhcswf.org. magenta yellow cyan black ILLINOIS Chicago Suburbs Our Women’s Health Team has privileges at the state-of-the-art facilities of Lee Memorial Health System Hospitals. A 3 On-Call rotation behind 6 CNMs with 115 deliveries per month. ContemporaryObgyn.net Independent ob/gyn practice of 6 MD’s and 4 CNM’s is seeking a BE/BC ob/gyn physician. New state of the art offices. Call 1/6. Level III NICU. Competitive salary and benefits. Please email CV to [email protected] Coastal Connecticut Hospital employed seeking two obgyn’s in coastal Connecticut community one hour to NYC associated with a modern and financially stable 106 bed hospital with new birthing unit and state-of-the-art technology. 1-3 call. Excellent salary, bonus and benefits. OBGYN Search, 800-831-5475, [email protected], www.obgynpractices.com 60 GEORGIA - NW METRO ATLANTA Illinois MFM Join nationally recognized 330 physician medical group in dynamic university community of 200,000 population two hours to Chicago and Indianapolis and three hours to St. Louis associated with a beautiful 325 bed hospital with Level III NICU doing 2500 annual deliveries in either consultative or obstetrical practice. Seeking two MFM physicians to join two physician department. 1-3 call. Excellent salary, bonus and benefits. OBGYN Search, 800-831-5475, [email protected] www.obgynpractices.com SEPTEMBER 2012 ES120469_obgyn0912_060_CL.pgs 08.29.2012 15:42 ADV RECRUITMENT NEW YORK CHAIR, OBSTETRICS & GYNECOLOGY “What does it take to find the career of a lifetime—Medicine of the Highest Order” The University of Rochester School of Medicine and Dentistry invites applications and nominations for the position of Chair in the Department of Obstetrics and Gynecology. The Department is a vibrant, multidisciplinary group, including approximately 50 full-time faculty members, a similar number of community-based faculty members, and many staff members including nursing, midwifery, social work, and several scientific disciplines. All enjoy close collaborations with faculty and programs across the Medical Center and region. Departmental divisions include general gynecology and obstetrics, gynecologic oncology, maternal-fetal medicine, reproductive endocrinology and infertility, urogynecology and reconstructive pelvic surgery, and a women’s health practice. Clinical programs span Strong Memorial Hospital, Highland Hospital, and two community sites: a Women’s Pavilion of subspecialty services, and a newly opened Women’s Health Center. Recognition for clinical care has included a 2010 National ACOG Service Award for patient safety and simulation. Educational programs are highly competitive, including outstanding recruits to the residency program and three subspecialty fellowships. Departmental education also has a prominent national and international presence, as its Peri-FACTS Academy is now used by more than 30,000 nurses, physicians, and students in over 800 hospitals and nursing schools. Thriving research programs include foci on the biology of pelvic floor disorders, genetics of vulvar disease, placental evaluation for the National Children’s Study, iron metabolism in the fetal-placental unit, biology of polycystic disease, and the immunology of placental infections. There are a wide range of community collaborations and outreach activities. The Department has three endowed Professorships, with two additional Professorships underway or planned by 2014. In 2011 the Department was ranked #32 in gynecology by US News and World Report. We seek candidates who are board certified in obstetrics and gynecology and have a strong record of leadership and administrative experience in the field. Candidates should have the outstanding leadership skills required to promote collaboration and excellence in patient care services, education, research, and community partnerships, and to foster programmatic growth in a medical center and university environment that prizes teamwork, innovation, and mentorship. The candidate must qualify for appointment as Professor at the University of Rochester. Applicants should apply on line at www.rochester.edu/jobopp, job number 176666 and forward their cover letter and curriculum vitae to Jeffrey Lyness, M.D., Senior Associate Dean for Academic Affairs at [email protected]. Phone number is 585-275-6321 The University of Rochester has a strong commitment to principles of diversity and, in that spirit, actively encourages applications from groups underrepresented in higher education Buffalo Area Rochester Suburb (Obgyn-CNM) Hospital employed obgyn position joining well established obgyn and Cnm with plans to recruit two obgyn physicians to the practice in attractive Buffalo family oriented suburb 45 minutes to downtown and airport associated with a stable 100 bed hospital with modern L/D doing 600 annual deliveries. 1-2 (1-3 future) call backing up CNM who takes all first call. Excellent salary, bonus and benefits. OBGYN Search 800-831-5475, [email protected], www.obgynpractices.com Employee position seeking obgyn and CNM to join two obgyn’s in desirable Rochester suburb associated with 261 bed teaching facility with 3300 annual deliveries and Level III NICU and new office located next door to hospital. 1-3 call. Excellent salary, bonus and benefits. OBGYN Search, 800-831-5475, [email protected], www.obgynpractices.com PENNSYLVANIA OHIO Superb OB/GYN Opportunity in Northeast Ohio! Seeking an OB/GYN physician to practice in Northeast Ohio. Join an established OB/GYN and his dedicated nursing staff in a very busy practice. This private practice is located in an excellent suburban community. They are associated with three hospitals in the area and have built a growing, thriving patient base. A competitive salary is offered as well as an attractive benefits package. Perfectly located within driving distance of Akron, Canton, and Cleveland. Candidates with J-1 visa may be considered. Please send CV’s to [email protected] We are a busy OB/GYN practice in central PA with 10 MDs/1 CRNP. Our call schedule is 1:6 which allows a decent quality of life. We do all our deliveries and surgeries at Good Samaritan Hospital. Lebanon is close to Philadelphia, Baltimore, New York City, and Washington, DC, but lacks the stress, hassles, and expense of a major metropolitan area. We have several arts festivals; we´re close to wineries; a farmer´s market is in town, and we´re next to a Rails to Trails and state parks. We´re also close to Hershey, famous for its chocolate, amusement park, and theatre. Competitive compensation package including medical liability, health, life, and disability insurance, and 401(k) profit-sharing plan. Applicants may also be eligible for a $75,000 signing bonus from the hospital. Send CV to: Recruitment Advertising Can Work For You! Trudi Noppenberger Women’s Health Center of Lebanon 300 Willow St. Lebanon, PA 17046 SEPTEMBER 2012 magenta yellow cyan black (717) 675-2561 direct (717) 273-0728 fax www.whclebanon.com [email protected] CONTEMPORARY OB/GYN 61 ES120470_obgyn0912_061_CL.pgs 08.29.2012 15:42 ADV RECRUITMENT PENNSYLVANIA VIRGINIA VIRGINIA RURAL/SUBURBAN PITTSBURGH Long standing, highly respected, busy OB/GYN practice looking for a full time associate to join 3 OB/GYN’s and Nurse Practitioner. 1:4 call. Affiliated with 400 bed Regional Medical Center with Level II nursery and approximately 1100 deliveries. Safe community with excellent schools and low cost of living. Less than one hour from Pittsburgh, the most livable city. Competitive salary and benefits package with tremendous earning potential as partner. Metro DC practice seeking BC/BE OB/GYN. Please email CV to [email protected]. Offering excellent income potential, amazing staff, autonomy, and a warm gratifying environment. WISCONSIN WISCONSIN Call Bonnie at (724) 843-8169 or fax CV to (724) 770-7922 OBSTETRIC/GYNECOLOGIC OPPORTUNITY NEAR MADISON! Central PA - Busy, mature practice looking for BE/BC OB/GYN Modern community hospital • University town • Pleasant community Good schools • Call 1/3 • Would consider 2 part-time physicians. New OR suite due to open 7/2012 and renovated OB suite in progress E-mail: [email protected] TEXAS • How does living 40 minutes outside of Madison sound to you? • Is it appealing to you to affiliate with a $100 million, leading-edge independent community hospital which was completed in 2006, offering the very best in technology? 4 State-of-the-art birthing suites with whirlpools and electronic fetal monitoring, each equipped with a computer for efficient patient care. 4 Experienced and skilled nursing staff with advanced training in labor, delivery and neonatal care. 4 Ranked 98 percentile in patient satisfaction! • A highly attractive salary and comprehensive benefits package are only a few of the desirable features of this practice opportunity. STRELCHECK & ASSOCIATES, INC. There is an outstanding opportunity for a BC/BE Maternal-Fetal medicine specialist to join an established and expanding practice with Covenant Medical Group in Lubbock, Texas. Covenant Maternal-Fetal Diagnostic Center is a specialty care practice dedicated to serving patients with specific maternal-fetal complications through counseling, consultations and the latest ultrasound technology. The practice currently operates under the direction of one MFM specialist that has almost 20 years of experience. The primarily outpatient consultative practice is affiliated with Covenant Women’s and Children’s Hospital, a tertiary care hospital that serves a large population base including West Texas and Eastern New Mexico. Covenant Women’s and Children’s Hospital has a Level III NICU. Inpatient services are complemented with the collaboration of an experienced obstetrical team and Laborist program. The designated Children’s Hospital includes a full team of Pediatric Subspecialties including Pediatric Cardiology and Surgery, as well as a Neonatology team. CONTACT Jane Dierberger at 800-243-4353 or [email protected] for immediate consideration. CONNECT with qualified leads and career professionals Post a job today Covenant Medical Group (CMG) is multi-specialty and employs over 160 physicians across West Texas and Eastern New Mexico. CMG offers a rich benefit package that includes a competitive compensation, an excellent benefit package, generous sign on bonus and a relocation allowance of $10,000. Interested Individuals can forward their CV to Covenant Medical Group Attn: Kelly Fortney at [email protected] For telephone inquires call 806-725-7875 Jacqueline Moran RECRUITMENT MARKETING ADVISOR (800) 225-4569, ext. 2762 [email protected] A D V E R T I S E T O D AY ! 62 magenta yellow cyan black ContemporaryObgyn.net SEPTEMBER 2012 ES120480_obgyn0912_062_CL.pgs 08.29.2012 15:43 ADV CALENDAR SEPTEMBER NOVEMBER 20-24: Obesity Society 30th Annual Scientific Meeting San Antonio, Texas CONTACT: http://www.obesity.org/ meetings-and-events/annualmeeting.htm 6-10: American Association of Gynecologic Laparoscopists (AAGL) 40th Global Congress of Minimally Invasive Gynecology Hollywood, Florida CONTACT: http://www.aagl.org/ annual-meeting 27-29: Society of OB/GYN Hospitalists 2nd Annual Clinical Meeting Denver, Colorado CONTACT: http://www. societyofobgynhospitalists.com JANUARY 2013 OCTOBER 3-6: North American Menopause Society 23rd Annual Meeting Orlando, Florida CONTACT: http://www.menopause.org/ 3-6: American Urogynecologic Society 33rd Annual Scientific Meeting Chicago, Illinois CONTACT: http://www.augsmeeting.org 17-20: The 79th Annual Meeting of the Central Association of Obstetricians and Gynecologists Chicago, Illinois CONTACT: http:///www.caog.org 14-16: 7th International DIP Symposium on Diabetes, Hypertension, Metabolic Syndrome, and Pregnancy Florence, Italy CONTACT: http://www2.kenes.com/ diabetes-pregnancy symposium/Pages/ General_Information.aspx APRIL 25-27: GOG Semi-Annual MeetingGynecologic Oncology Group San Diego, California CONTACT: http://www.gog.org/ meetinginformation.html 8-10: 39th Annual SGS Scientific Meeting-Society of Gynecologic Surgeons Charleston, South Carolina CONTACT: http://www.sgsonline.org/ futuremeetings.php MAY FEBRUARY 3-9: Society for Maternal-Fetal Medicine 33rd Annual Meeting—The Pregnancy Meeting San Francisco, California CONTACT: https://www.smfm.org/ Annual%20Meeting%20Page. cfm?ht=me 4-8: 61st Annual Clinical MeetingAmerican Congress of Obstetricians and Gynecologists New Orleans, Louisiana CONTACT: http://classic.acog.org/acm/ HAVE AN EVENT? MARCH E-MAIL your event to: [email protected] 10-13: The 2013 Annual Meeting On Women’s Cancer Los Angeles, California CONTACT: http://wwwwww.sgo.org Please type “Event” in the subject line. ADVERTISER INDEX | Companies featured in this issue To obtain additional information about products and services advertised in this issue, use the contact information below. This index is provided as an additional service. The publisher does not assume any liability for errors or omissions. APPLIED MEDICAL FUJIREBIO DIAGNOSTICS INC TEXAS CHILDRENS HOSPITAL www.appliedmedical.com www.he4test.com www.fetal.texaschildrens.org Alexis..........................................................15 Kii.................................................................53 HE4.............................................................17 Fetal Center................................................ 7 www.appliedmedical.com HOLOGIC ASTELLAS PHARMA US, INC Novasure...................................................31 www.hologic.com UNIVERSITY OF PITTSBURGH MEDICAL CENTER www.astellas.us LACLEDE INC www.upmcphysicianresources.com/ specialties/gynecology www.luvenacare.com VERMILLION INC GYRUS ACMI www.ova-1.com Myrbetriq...................................................11 BAYER HEALTHCARE LLC Citracal.......................................................41 www.citracalpro.com CHROMOGENEX iLipo............................................................29 Luvena.................................................22-23 Medical Reputation.................................51 OVA1.................................................. CVTIP Innovate.....................................................47 www.olympusamerica.com/less WALLACH SURGICAL DEVICES COOPER SURGICAL PFIZER INC www.wallachsurgical.com www.coopersurgical.com www.toviazhcp.com www.ilipo.com Filshie........................................................... 9 Toviaz...................................................33-34 Her Option.........................................18-19 Premarin.......................................... 64-CV4 www.HerOption.com www.premarinvaginalcreamhcp.com FERRING PHARMACEUTICALS ROCHE DIAGNOSTICS www.lysteda.com www.hpv16and18.com Lysteda................................................43-44 Colposcopes............................................37 HPV Test...................................................25 september 2012 CONTEMPORARY OB/GYN 63 PREMARIN® (conjugated estrogens tablets, USP) BRIEF SUMMARY: This is only a brief summary of prescribing information. For current full prescribing information, please visit www.PremarinHCP.com. Rx only WARNING: ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. (See WARNINGS, Malignant Neoplasms, Endometrial cancer.) Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders and Probable Dementia.) The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg]-alone, relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders.) The WHI Memory Study (WHIMS) estrogen-alone ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg)-alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL STUDIES and WARNINGS, Probable Dementia and PRECAUTIONS, Geriatric Use.) In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders and Probable Dementia.) The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo. (See CLINICAL STUDIES and WARNINGS, Cardiovascular Disorders.) The WHIMS estrogen plus progestin ancillary study of the WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women. (See CLINICAL STUDIES and WARNINGS, Probable Dementia and PRECAUTIONS, Geriatric Use.) Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer. (See CLINICAL STUDIES and WARNINGS, Malignant Neoplasms, Breast cancer.) In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. INDICATIONS AND USAGE PREMARIN therapy is indicated in the: sª Treatment of moderate to severe vasomotor symptoms due to menopause. sª Treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause. When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered. sª Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure. sª Treatment of breast cancer (for palliation only) in appropriately selected women and men with metastatic disease. sª Treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only). sª Prevention of postmenopausal osteoporosis. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medications should be carefully considered. The mainstays for decreasing the risk of postmenopausal osteoporosis are weight-bearing exercise, adequate calcium and vitamin D intake, and when indicated, pharmacologic therapy. Postmenopausal women require an average of 1500 mg per day of elemental calcium. Therefore, when not contraindicated, calcium supplementation may be helpful for women with suboptimal dietary intake. Vitamin D supplementation of 400-800 IU per day may also be required to ensure adequate daily intake in postmenopausal women. CONTRAINDICATIONS PREMARIN therapy should not be used in individuals with any of the following conditions: sª Undiagnosed abnormal genital bleeding. sª Known, suspected, or history of breast cancer except in appropriately selected patients being treated for metastatic disease. sª Known or suspected estrogen-dependent neoplasia. sª Active DVT, PE, or a history of these conditions. sª Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions. sª Known anaphylactic reaction or angioedema to PREMARIN tablets. sª Known liver dysfunction or disease. sª Known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders. sª Known or suspected pregnancy. WARNINGS See BOXED WARNINGS. 1. Cardiovascular Disorders An increased risk of stroke and DVT has been reported with estrogen-alone therapy. An increased risk of PE, DVT, stroke, and MI has been reported with estrogen plus progestin therapy. Should any of these events occur or be suspected, estrogen with or without progestin therapy should be discontinued immediately. Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (VTE) (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately. a. Stroke In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). (See CLINICAL STUDIES.) The increase in risk was demonstrated in year 1 and persisted. Should a stroke occur or be suspected, estrogen-alone therapy should be discontinued immediately. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years). In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women in the same age group receiving placebo (33 versus 25 per 10,000 women-years). (See CLINICAL STUDIES.) The increase in risk was demonstrated after the first year and persisted. Should a stroke occur or be suspected, estrogen plus progestin therapy should be discontinued immediately. black b. Coronary heart disease In the WHI estrogen-alone substudy, no overall effect on CHD events (defined as nonfatal MI, silent MI, or CHD death) was reported in women receiving estrogen-alone compared to placebo. (See CLINICAL STUDIES.) Subgroup analyses of women 50 to 59 years of age suggest a statistically non-significant reduction in CHD events (CE [0.625 mg]-alone compared to placebo) in women less than 10 years since menopause (8 versus 16 per 10,000 women-years). In the WHI estrogen plus progestin substudy, there was a statistically non-significant increased risk of CHD events reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women years). An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5. In postmenopausal women with documented heart disease (n = 2,763, average age 66.7 years), in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/Progestin Replacement Study; HERS), treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand three hundred and twenty one (2,321) women from the original HERS trial agreed to participate in an open-label extension of HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE plus MPA group and the placebo group in the HERS, the HERS II, and overall. c. Venous thromboembolism In the WHI estrogen-alone substudy, the risk of VTE (DVT and PE), was increased for women receiving daily CE (0.625 mg)-alone compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women years). The increase in VTE risk was demonstrated during the first 2 years. (See CLINICAL STUDIES.) Should a VTE occur or be suspected, estrogen-alone therapy should be discontinued immediately. In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE was reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women years) were also demonstrated. The increase in VTE risk was demonstrated during the first year and persisted. (See CLINICAL STUDIES.) Should a VTE occur or be suspected, estrogen plus progestin therapy should be discontinued immediately. If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. 2. Malignant Neoplasms a. Endometrial cancer An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in a woman with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with the use of estrogens for less than 1 year. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more, and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Adding a progestin to postmenopausal estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. b. Breast cancer The most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the WHI substudy of daily CE (0.625 mg)-alone. In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE (0.625 mg)-alone was not associated with an increased risk of invasive breast cancer (relative risk [RR] 0.80) (See CLINICAL STUDIES). The most important randomized clinical trial providing information about breast cancer in estrogen plus progestin users is the WHI substudy of daily CE (0.625 mg) plus MPA (2.5 mg). After a mean follow-up of 5.6 years, the estrogen plus progestin substudy reported an increased risk of invasive breast cancer in women who took daily CE plus MPA. In this substudy, prior use of estrogen-alone or estrogen plus progestin therapy was reported by 26 percent of the women. The relative risk of invasive breast cancer was 1.24 and the absolute risk was 41 versus 33 cases per 10,000 women-years, for CE plus MPA compared with placebo. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years, for CE plus MPA compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 versus 36 cases per 10,000 women-years for CE plus MPA compared with placebo. In the same substudy, invasive breast cancers were larger, were more likely to be node positive, and were diagnosed at a more advanced stage in the CE (0.625 mg) plus MPA (2.5 mg) group compared with the placebo group. Metastatic disease was rare, with no apparent difference between the two groups. Other prognostic factors, such as histologic subtype, grade and hormone receptor status did not differ between the groups. (See CLINICAL STUDIES.) Consistent with the WHI clinical trial, observational studies have also reported an increased risk of breast cancer for estrogen plus progestin therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. The risk increased with duration of use, and appeared to return to baseline over about 5 years after stopping treatment (only the observational studies have substantial data on risk after stopping). Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen plus progestin therapy as compared to estrogen-alone therapy. However, these studies have not found significant variation in the risk of breast cancer among different estrogen plus progestin combinations, doses, or routes of administration. The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation. All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results. c. Ovarian cancer The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE plus MPA versus placebo was 1.58 (95 percent CI, 0.77 – 3.24). The absolute risk for CE plus MPA versus placebo was 4 versus 3 cases per 10,000 women-years. In some epidemiologic studies, the use of estrogen plus progestin and estrogen-only products, in particular for 5 or more years, has been associated with an increased risk of ovarian cancer. However, the duration of exposure associated with increased risk is not consistent across all epidemiologic studies and some report no association. 3. Probable Dementia In the WHIMS estrogen-alone ancillary study of WHI, a population of 2,947 hysterectomized women 65 to 79 years of age was randomized to daily CE (0.625 mg)-alone or placebo. After an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent CI, 0.83-2.66). The absolute risk of probable dementia for CE-alone versus placebo was 37 versus 25 cases per 10,000 women-years. (See CLINICAL STUDIES and PRECAUTIONS, Geriatric Use.) In the WHIMS estrogen plus progestin ancillary study of WHI, a population of 4,532 postmenopausal women 65 to 79 years of age was randomized to daily CE (0.625 mg) plus MPA (2.5 mg) or placebo. After an average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95 percent CI, 1.21-3.48). The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 cases per 10,000 women-years. (See CLINICAL STUDIES and PRECAUTIONS, Geriatric Use.) When data from the two populations in the WHIMS estrogen-alone and estrogen plus progestin ancillary studies were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent CI, 1.19-2.60). Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women. (See PRECAUTIONS, Geriatric Use.) 4. Gallbladder Disease A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported. (continued on next page) ES110962_OBGYN0912_064_FP.pgs 08.20.2012 23:32 ADV 5. Hypercalcemia Estrogen administration may lead to severe hypercalcemia in patients with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level. 6. Visual Abnormalities Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued. 7. Anaphylactic Reaction and Angioedema Cases of anaphylaxis, which developed within minutes to hours after taking PREMARIN and require emergency medical management, have been reported in the postmarketing setting. Skin (hives, pruritis, swollen lips-tongue-face) and either respiratory tract (respiratory compromise) or gastrointestinal tract (abdominal pain, vomiting) involvement has been noted. Angioedema involving the tongue, larynx, face, hands, and feet requiring medical intervention has occurred postmarketing in patients taking PREMARIN. If angioedema involves the tongue, glottis, or larynx, airway obstruction may occur. Patients who develop an anaphylactic reaction with or without angioedema after treatment with PREMARIN should not receive PREMARIN again. 8. Hereditary Angioedema Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema. PRECAUTIONS A. General 1. Addition of a progestin when a woman has not had a hysterectomy Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration, or daily with estrogen in a continuous regimen, have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include an increased risk of breast cancer. 2. Elevated blood pressure In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical trial, a generalized effect of estrogen therapy on blood pressure was not seen. 3. Hypertriglyceridemia In women with pre-existing hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Consider discontinuation of treatment if pancreatitis occurs. 4. Hepatic impairment and/or past history of cholestatic jaundice Estrogens may be poorly metabolized in patients with impaired liver function. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised, and in the case of recurrence, medication should be discontinued. 5. Hypothyroidism Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range. 6. Fluid retention Estrogens may cause some degree of fluid retention. Women with conditions that might be influenced by this factor, such as cardiac or renal dysfunction, warrant careful observation when estrogens are prescribed. 7. Hypocalcemia Estrogen therapy should be used with caution in individuals with hypoparathyroidism as estrogen-induced hypocalcemia may occur. 8. Exacerbation of endometriosis A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy. For women known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered. 9. Exacerbation of other conditions Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions. B. Patient Information Physicians are advised to discuss the contents of the PATIENT INFORMATION leaflet with patients for whom they prescribe PREMARIN. C. Laboratory Tests Serum FSH and estradiol levels have not been shown to be useful in the management of moderate to severe vasomotor symptoms and moderate to severe symptoms of vulvar and vaginal atrophy. Laboratory parameters may be useful in guiding dosage for the treatment of hypoestrogenism due to hypogonadism, castration and primary ovarian failure. D. Drug-Laboratory Test Interactions 1. Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of anti-factor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity. 2. Increased thyroid binding globulin (TBG) levels leading to increased circulating total thyroid hormone levels as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay) or T3 levels by radioimmunoassay. T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Women on thyroid replacement therapy may require higher doses of thyroid hormone. 3. Other binding proteins may be elevated in serum, for example, corticosteroid binding globulin (CBG), SHBG, leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin). 4. Increased plasma high-density lipoprotein (HDL) and HDL2 cholesterol subfraction concentrations, reduced low-density lipoprotein (LDL) cholesterol concentrations, increased triglyceride levels. 5. Impaired glucose tolerance. E. Carcinogenesis, Mutagenesis, Impairment of Fertility (See BOXED WARNINGS, WARNINGS, and PRECAUTIONS.) Long-term continuous administration of natural and synthetic estrogens in certain animal species increases the frequency of carcinomas of the breast, uterus, cervix, vagina, testis, and liver. F. Pregnancy PREMARIN should not be used during pregnancy. (See CONTRAINDICATIONS.) There appears to be little or no increased risk of birth defects in children born to women who have used estrogens and progestins as an oral contraceptive inadvertently during early pregnancy. G. Nursing Mothers PREMARIN should not be used during lactation. Estrogen administration to nursing women has been shown to decrease the quantity and quality of the breast milk. Detectable amounts of estrogens have been identified in the breast milk of women receiving estrogens. Caution should be exercised when PREMARIN is administered to a nursing woman. H. Pediatric Use Estrogen therapy has been used for the induction of puberty in adolescents with some forms of pubertal delay. Safety and effectiveness in pediatric patients have not otherwise been established. Large and repeated doses of estrogen over an extended time period have been shown to accelerate epiphyseal closure, which could result in short stature if treatment is initiated before the completion of physiologic puberty in normally developing children. If estrogen is administered to patients whose bone growth is not complete, periodic monitoring of bone maturation and effects on epiphyseal centers is recommended during estrogen administration. Estrogen treatment of prepubertal girls also induces premature breast development and vaginal cornification, and may induce vaginal bleeding. In boys, estrogen treatment may modify the normal pubertal process and induce gynecomastia. (See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION.) black I. Geriatric Use There have not been sufficient numbers of geriatric patients involved in studies utilizing PREMARIN to determine whether those over 65 years of age differ from younger subjects in their response to PREMARIN. The Women’s Health Initiative Study In the WHI estrogen-alone substudy (daily CE [0.625 mg]-alone versus placebo), there was a higher relative risk of stroke in women greater than 65 years of age. (See CLINICAL STUDIES.) In the WHI estrogen plus progestin substudy (daily CE [0.625 mg] plus MPA [2.5 mg] versus placebo), there was a higher relative risk of nonfatal stroke and invasive breast cancer in women greater than 65 years of age. (See CLINICAL STUDIES.) The Women’s Health Initiative Memory Study In the WHIMS ancillary studies of postmenopausal women 65 to 79 years of age, there was an increased risk of developing probable dementia in women receiving estrogen-alone or estrogen plus progestin when compared to placebo. (See CLINICAL STUDIES and WARNINGS, Probable Dementia.) Since both ancillary studies were conducted in women 65 to 79 years of age, it is unknown whether these findings apply to younger postmenopausal women. (See CLINICAL STUDIES and WARNINGS, Probable Dementia.) ADVERSE REACTIONS See BOXED WARNINGS, WARNINGS, and PRECAUTIONS. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. During the first year of a 2-year clinical trial with 2,333 postmenopausal women between 40 and 65 years of age (88 percent Caucasian), 1,012 women were treated with conjugated estrogens and 332 were treated with placebo. The following table summarizes adverse events that occurred at a rate of ≥ 5 percent. NUMBER (%) OF PATIENTS REPORTING ≥ 5 PERCENT TREATMENT EMERGENT ADVERSE EVENTS --Conjugated Estrogens Treatment Group- Body System 0.625 mg 0.45 mg 0.3 mg Placebo Adverse event Any adverse event Body as a Whole Abdominal pain Accidental injury Asthenia Back pain Flu syndrome Headache Infection Pain Digestive System Diarrhea Dyspepsia Flatulence Nausea Musculoskeletal System Arthralgia Leg cramps Myalgia Nervous System Depression Dizziness Insomnia Nervousness Respiratory System Cough increased Pharyngitis Rhinitis Sinusitis Upper respiratory infection Skin and Appendages Pruritus Urogenital System Breast pain Leukorrhea Vaginal hemorrhage Vaginal moniliasis Vaginitis (n = 348) 323 (93%) 56 (16%) 21 (6%) 25 (7%) 49 (14%) 37 (11%) 90 (26%) 61 (18%) 58 (17%) (n = 338) 305 (90%) 50 (15%) 41 (12%) 23 (7%) 43 (13%) 38 (11%) 109 (32%) 75 (22%) 61 (18%) (n = 326) 292 (90%) 54 (17%) 20 (6%) 25 (8%) 43 (13%) 33 (10%) 96 (29%) 74 (23%) 66 (20%) (n = 332) 281 (85%) 37 (11%) 29 (9%) 16 (5%) 39 (12%) 35 (11%) 93 (28%) 74 (22%) 61 (18%) 21 (6%) 33 (9%) 24 (7%) 32 (9%) 25 (7%) 32 (9%) 23 (7%) 21 (6%) 19 (6%) 36 (11%) 18 (6%) 21 (6%) 21 (6%) 46 (14%) 9 (3%) 30 (9%) 47 (14%) 19 (5%) 18 (5%) 42 (12%) 23 (7%) 18 (5%) 22 (7%) 11 (3%) 29 (9%) 39 (12%) 7 (2%) 25 (8%) 25 (7%) 19 (5%) 21 (6%) 12 (3%) 27 (8%) 20 (6%) 25 (7%) 17 (5%) 17 (5%) 12 (4%) 24 (7%) 6 (2%) 22 (7%) 17 (5%) 33 (10%) 7 (2%) 13 (4%) 35 (10%) 21 (6%) 22 (6%) 42 (12%) 22 (7%) 35 (10%) 30 (9%) 36 (11%) 34 (10%) 14 (4%) 40 (12%) 31 (10%) 24 (7%) 28 (9%) 14 (4%) 38 (11%) 42 (13%) 24 (7%) 35 (11%) 14 (4%) 17 (5%) 16 (5%) 7 (2%) 38 (11%) 18 (5%) 47 (14%) 20 (6%) 24 (7%) 41 (12%) 22 (7%) 14 (4%) 18 (5%) 20 (6%) 24 (7%) 13 (4%) 7 (2%) 17 (5%) 16 (5%) 29 (9%) 9 (3%) 0 6 (2%) 4 (1%) Postmarketing Experience The following additional adverse reactions have been identified during post approval use of PREMARIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Genitourinary System Abnormal uterine bleeding, dysmenorrhea or pelvic pain, increase in size of uterine leiomyomata, vaginitis, including vaginal candidiasis, change in cervical secretion, ovarian cancer, endometrial hyperplasia, endometrial cancer, leukorrhea. Breast Tenderness, enlargement, pain, discharge, galactorrhea, fibrocystic breast changes, breast cancer, gynecomastia in males. Cardiovascular Deep and superficial venous thrombosis, pulmonary embolism, thrombophlebitis, myocardial infarction, stroke, increase in blood pressure. Gastrointestinal Nausea, vomiting, abdominal pain, bloating, cholestatic jaundice, increased incidence of gallbladder disease, pancreatitis, enlargement of hepatic hemangiomas, ischemic colitis. Skin Chloasma or melasma that may persist when drug is discontinued, erythema multiforme, erythema nodosum, loss of scalp hair, hirsutism, pruritus, rash. Eyes Retinal vascular thrombosis, intolerance to contact lenses. Central Nervous System Headache, migraine, dizziness, mental depression, nervousness, mood disturbances, irritability, exacerbation of epilepsy, dementia, possible growth potentiation of benign meningioma. Miscellaneous Increase or decrease in weight, glucose intolerance, aggravation of porphyria, edema, arthralgias, leg cramps, changes in libido, urticaria, exacerbation of asthma, increased triglycerides, hypersensitivity. Additional postmarketing adverse reactions have been reported in patients receiving other forms of hormone therapy. This brief summary is based on PREMARIN Prescribing Information LAB-0467-3.0, Rev. 10/11. © 2012 Pfizer Inc. All rights reserved. April 2012 ES110961_OBGYN0912_CV3_FP.pgs 08.20.2012 23:32 ADV Don’t let moderate to severe hot flashes and VVA,* as well as bone loss, gang up on your menopausal patients. 1-3 To learn about the WHI estrogen alone substudy and why PREMARIN may be right for the appropriate, postmenopausal, hysterectomized woman in her 50s, visit www.PremarinHCP.com/age *Vulvar and vaginal atrophy. INDICATION: PREMARIN® (conjugated estrogens tablets, USP) is indicated in the treatment of moderate to severe vasomotor symptoms due to menopause, treatment of moderate to severe symptoms of vulvar and vaginal atrophy due to menopause, and the prevention of postmenopausal osteoporosis. IMPORTANT SAFETY INFORMATION: There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. The Women’s Health Initiative (WHI) estrogen alone substudy reported increased risks of stroke and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) (0.625 mg) alone, relative to placebo. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke, and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) (2.5 mg), relative to placebo. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE with or without MPA, and other combinations and dosage forms of estrogens with or without progestins. The WHI Memory Study (WHIMS) estrogen alone study reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg) alone, relative to placebo. The WHIMS estrogen plus progestin study reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether these findings apply to younger postmenopausal women. PRM00442/PRM425503-01 magenta yellow cyan black © 2012 Pfizer Inc. The WHI estrogen plus progestin substudy demonstrated an increased risk of invasive breast cancer. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Estrogens with or without progestins should not be used for the prevention of cardiovascular disease or dementia. PREMARIN® (conjugated estrogens tablets, USP) should not be used in women with any of the following conditions: undiagnosed abnormal genital bleeding; known, suspected, or a history of breast cancer; known or suspected estrogendependent neoplasia; active deep vein thrombosis, pulmonary embolism, or a history of these conditions; active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions; known anaphylactic reactions or angioedema; known liver dysfunction or disease; known thrombophilic disorders; known or suspected pregnancy. When prescribing solely for the symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered. When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and for whom non-estrogen medications are not considered appropriate. In a clinical trial, the most commonly reported (≥5%) adverse events for PREMARIN tablets that were statistically different than placebo included vaginal moniliasis, vaginitis, vaginal bleeding, dysmenorrhea, and leg cramps. References: 1. Stearns V, Ullmer L, López JF, Smith Y, Isaacs C, Hayes DF. Hot flushes. Lancet. 2002;360(9348):1851-1861. 2. National Institutes of Health. National Institutes of Health State-of-the-Science Conference statement: management of menopause-related symptoms. Ann Intern Med. 2005;142(12 Pt 1):1003-1013. 3. Finkelstein JS. Osteoporosis. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia, PA: Saunders; 2004:1547-1555. Please see Brief Summary of Full Prescribing Information, including boxed warning, on the following pages. All rights reserved. Printed in USA/March 2012 ES110964_OBGYN0912_CV4_FP.pgs 08.20.2012 23:32 ADV
